Changing Mad2 Levels Affects Chromosome Segregation and Spindle Assembly Checkpoint Control in Female Mouse Meiosis I

The spindle assembly checkpoint (SAC) ensures correct separation of sister chromatids in somatic cells and provokes a cell cycle arrest in metaphase if one chromatid is not correctly attached to the bipolar spindle. Prolonged metaphase arrest due to overexpression of Mad2 has been shown to be deleterious to the ensuing anaphase, leading to the generation of aneuploidies and tumorigenesis. Additionally, some SAC components are essential for correct timing of prometaphase. In meiosis, we and others have shown previously that the Mad2-dependent SAC is functional during the first meiotic division in mouse oocytes. Expression of a dominant-negative form of Mad2 interferes with the SAC in metaphase I, and a knock-down approach using RNA interference accelerates anaphase onset in meiosis I. To prove unambigiously the importance of SAC control for mammalian female meiosis I we analyzed oocyte maturation in Mad2 heterozygote mice, and in oocytes overexpressing a GFP-tagged version of Mad2. In this study we show for the first time that loss of one Mad2 allele, as well as overexpression of Mad2 lead to chromosome missegregation events in meiosis I, and therefore the generation of aneuploid metaphase II oocytes. Furthermore, SAC control is impaired in mad2+/− oocytes, also leading to the generation of aneuploidies in meiosis I

Ultrafast-laser powder bed fusion of oxygen-deficient Nb_(2)O_(5) ceramics with highly improved electrical properties

In this work, Nb_(2)O_(5) layers with highly improved electrical properties respect to pristine material have been produced by ultrafast-laser powder bed fusion process. The conditions required for producing uniform and compact layers of Nb_(2)O_(5) from powder material have been studied and optimized. It has been established that ultrafast-laser irradiation, performed in air at room temperature, leads to the formation of dense Nb_(2)O_(5) layers with the high temperature monoclinic crystal structure (H- Nb_(2)O_(5)) but oxygen deficient. The layers show a preferential crystal orientation with the short axis of the monoclinic structure lying in the structure plane. This preferential orientation can be controlled by the laser irradiation conditions. Anisotropic resistivity has been observed as a consequence of the induced microstructure, while the overall material resistivity is decreased by more than eight orders of magnitude due to the oxygen deficiency. These results indicate that it is feasible to use ultrafast laser processing to promote hightemperature non-stoichiometric niobium oxide phases in a few seconds and with low energy consumption. The highly improved electrical properties of the laser irradiated Nb_(2)O_(5) layers are extremely interesting for different electronic and sensing applications

Evolution of whispering gallery modes in Li-doped ZnO hexagonal micro- and nanostructures

The investigated materials have great potential for integrated optoelectronic devices. The possibility to integrate them into the same material as optical resonator and light guide opens the door to the fabrication of highly compact devices. The formation of optical cavities in Li-doped ZnO nanostructures was investigated. By means of the vapor-solid method, long micro- and nanostructures with a hexagonal cross-section were grown. These morphologies were favorable for Fabry-Perot and whispering gallery modes to appear. A variety of structures with different sections was studied using mu-photoluminescence in both the transverse electric (TE) and transverse magnetic (TM) polarizations, showing well-pronounced optical resonant modes. The results showed a dominance of whispering gallery modes that were in good agreement with the calculated refractive index. The quality factor (Q) and finesse (F) were estimated, which demonstrated the quality of Li:ZnO structures as optical cavities

Plk1 overexpression induces chromosomal instability and suppresses tumor development

Polo-like kinase 1 (Plk1) is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression results in abnormal chromosome segregation and cytokinesis, generating polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge, in a Plk1 kinase-dependent manner. In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. In patients, Plk1 overexpression correlates with improved survival in specific breast cancer subtypes. Therefore, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor-suppressive properties by perturbing mitotic progression and cytokinesis.We are indebted to Stephen Taylor for the Sgo1 antibody. We thank Simone Kraut, Jessica Steiner, and the DKFZ light microscopy unit for excellent technical assistance. The results published here are in part based on data generated by TCGA pilot project (https://cancergenome.nih.gov/established by the NCI and the National Human Gen- ome Research Institute. The data were retrieved through dbGaP authorization (accession no. phs000178.v9.p8). S.V.V. was supported by the Marie Curie Network Ploidynet, funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Grant Agreement #316964. L.S. is supported by a postdoctoral fellowship from Funda- cion Ramon Areces. Work in the R.S. laboratory was supported by an ERC starting grant (#281614), Marie Curie PCIG09-GA-2011 –293745 and the Howard Hughes Medical Institute. G.d.C. is funded by AECC Scientific Foundation (LABAE16017DECA). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2015 –69920-R cofunded by ERDF-EU), Worldwide Cancer Research (WCR no. 150278), and Comunidad de Madrid (iLUNG-CM; B2017/BMD3884). The CNIO is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0510).S

Current practices and challenges in the diagnosis and management of pku in Latin America: A multicenter survey

This study aimed to describe the current practices in the diagnosis and dietary management of phenylketonuria (PKU) in Latin America, as well as the main barriers to treatment. We developed a 44-item online survey aimed at health professionals. After a pilot test, the final version was sent to 25 practitioners working with inborn errors of metabolism (IEM) in 14 countries. Our results include 22 centers in 13 countries. Most countries (12/13) screened newborns for PKU. Phenylalanine (Phe) targets at different ages were very heterogeneous among centers, with greater consistency at the 0–1 year age group (14/22 sought 120–240 µmol/L) and the lowest at >12 years (10 targets reported). Most countries had only unflavored powdered amino acid substitutes (10/13) and did not have low-protein foods (8/13). Only 3/13 countries had regional databases of the Phe content of foods, and only 4/22 centers had nutrient analysis software. The perceived obstacles to treatment were: low purchasing power (62%), limited/insufficient availability of low-protein foods (60%), poor adherence, and lack of technical resources to manage the diet (50% each). We observed a heterogeneous scenario in the dietary management of PKU, and most countries experienced a lack of dietary resources for both patients and health professionals.Fil: Poloni, Soraia. Hospital de Clínicas de Porto Alegre; BrasilFil: Dos Santos, Bruna Bento. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Specola, Norma. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Pereyra, Marcela. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Saborío Rocafort, Manuel. Universidad de Costa Rica; Costa RicaFil: Salazar, María Florencia. Universidad de Chile; ChileFil: Leal-Witt, María Jesús. Universidad de Chile; ChileFil: Castro, Gabriela. Universidad de Chile; ChileFil: Peñaloza, Felipe. Universidad de Chile; ChileFil: Wong, Sunling Palma. Hospital Nacional de Niños; Costa RicaFil: Badilla Porras, Ramsés. Hospital Nacional de Niños; Costa RicaFil: Ortiz Paranza, Lourdes. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Sanabria, Marta Cristina. Hospital de Clínicas; ParaguayFil: Vela Amieva, Marcela. Instituto Nacional de Pediatría; MéxicoFil: Morales, Marco. No especifíca;Fil: Caro Naranjo, Amanda Rocío. Pontificia Universidad Javeriana; ColombiaFil: Mahfoud, Antonieta. Pontificia Universidad Javeriana; ColombiaFil: Colmenares, Ana Rosa. Hospital Clinica Caracas-Materno Infantil de Caricuao; VenezuelaFil: Lemes, Aida. Instituto de Seguridad Social; UruguayFil: Sotillo Lindo, José Fernando. Hospital de especialidades Pediátricas “Omar Torrijos Herrera"; PanamáFil: Perez, Ceila. Robert Reid Cabral Children’s Hospital; República DominicanaFil: Martínez Rey, Laritza. Centro Nacional de Genética Médica; CubaFil: Zayas Torriente, Georgina María. Centro de Nutrición e Higiene de los Alimentos del Instituto Nacional de Higiene, Epidemiología y Microbiología; CubaFil: Farret Refosco, Lilia. Hospital de Clínicas de Porto Alegre; BrasilFil: Doederlein Schwartz, Ida Vanessa. Universidade Federal do Rio Grande do Sul; Brasil. Hospital de Clínicas de Porto Alegre; BrasilFil: Cornejo, Veronica. Universidad de Chile; Chil

Herramienta integral y de bajo coste para el desarrollo de prácticas remotas para las asignaturas de Ciencias e Ingeniería

Los laboratorios remotos, en los que los alumnos interactúan con los dispositivos reales a través de Internet, incrementa el tiempo de uso de dichos dispositivos por parte de los alumnos y el número de pruebas que pueden realizar durante las experiencias. Sin embargo, para implementarlos, los docentes habitualmente tienen que saber utilizar una serie de tecnologías diferentes, que dificultan su puesta en marcha y mantenimiento. Para paliar estos problemas, en este Proyecto de Innovación y Mejora de la Calidad Docente (PIMCD) se ha desarrollado una nueva metodología desde la que se centraliza la puesta en marcha de todo el laboratorio desde una única herramienta (Easy JavaScript Simulations, EJsS), que sirve tanto para gestionar el código mediante el que se interactúa con los dispositivos, el servidor que da acceso remoto a la práctica, y la interfaz gráfica con la que los alumnos interactúan con los dispositivos. Además, es importante resaltar que es una metodología de bajo coste, ya que desde el punto de vista del proceso de conversión de un laboratorio presencial ya existente en uno remoto, solo necesita una Raspberry PI para desplegar todo el software del laboratorio. Además, en este proyecto también se presentan un conjunto de experiencias desarrolladas con las mismas, que ya están siendo utilizadas por los alumnos en diferentes asignaturas de Ingeniería Electrónica de Comunicaciones y un nuevo laboratorio remoto de Robótica que se pondrá en marcha el curso que viene

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Control del ciclo celular y del desarrollo de tumores por las quinasas dependientes de ciclinas Cdk4 y Cdk6

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Ciencias. Departamento de Biología Molecular. Fecha de lectura: 31-10-200

Growth and characterization of Zr doped ZnO structures on femtosecond laser induced periodic structures on different substrates

“Nano-scale characterization for cutting-edge materials research and sustainable materials development”, Dresden, Germany, August 30 th, 2019Doped ZnO nanostructures have been widely investigated for their electrical and optical properties. It is one of the most used transparent conducting oxide (TCO) with low resistivity (¿10¿3¿¿¿¿¿), high transparency (>80%) and high carrier concentration (¿1020¿¿¿¿¿3). Doping with Zr is proposed because of the similar ionic size of Zr4+ and Zn2+. That means the lattice distortions are minimized while the thermal and the chemical stability are improved being a promising alternative for high temperature working devices [1]. Furthermore, ZnO:Zr has shown enhanced photocatalytic properties [2]. In this work, Zr doped ZnO structures have been grown on different oriented Silicon substrates by a vapour-solid method under an Argon flux as is shown in Figure 1a. Mixtures of ZnS and ZrO2 in different percentages were used as precursors. Silicon and substrates have been also irradiated under certain conditions by a femtosecond laser operating at 1030nm with a pulse duration of 340 fs (Figure 1b). The irradiation of the substrates generates laser periodic surface structures (LIPSS) which depending on the irradiation condition could be amorphous or ablative structures [3]. The influence of the processed surface in the growth has been studied according to different parameters as the thermal treatment duration, percentage of doping, type of induced LIPSS and substrate orientation among others. Scanning Electron Microscopy has been used to analyze the morphology of the structures and Photoluminescence measurements provide information about the luminescence properties and the amount of defects in the structure giving a hint about the influence of the different parameters used in the growing process. References [1] S. Herodotou, R. Treharne, K. Durose, G. Tatlock, R. Potter, Materials 2015, 8, 10. [2] N. Clament Segaya Selvam, J. Judith Vijaya, L. John Kennedy, Industrial & Engineering Chemistry Research 2012, 51, 50. [3] D. Puerto, M. Garcia-Lechuga, A. Garcia-Leis, S. Sanchez-Cortes, J. Solis, J. Siegel, Nanotechnology 2016, 27, 26

Evolution of whispering gallery modes in Li-Doped ZnO hexagonal micro- and nanostructures

13 pags., 10 figs., 2 tabs.The formation of optical cavities in Li-doped ZnO nanostructures was investigated. By means of the vapor¿solid method, long micro- and nanostructures with a hexagonal cross-section were grown. These morphologies were favorable for Fabry-Pérot and whispering gallery modes to appear. A variety of structures with different sections was studied using µ-photoluminescence in both the transverse electric (TE) and transverse magnetic (TM) polarizations, showing well-pronounced optical resonant modes. The results showed a dominance of whispering gallery modes that were in good agreement with the calculated refractive index. The quality factor (Q) and finesse (F) were estimated, which demonstrated the quality of Li:ZnO structures as optical cavitiesThe authors are grateful to the Complutense University of Madrid and Banco Santander for support via the project UCM-Santander 2019 (PR87/19-22613) and to the Spanish Ministry of Science, Innovation and Universities for support via the project MINECO/FEDER-MAT2015-65274-R. B.S. acknowledges financial support from Comunidad de Madrid and Complutense University of Madrid (Ayudas del Programa de Atracción de Talento 2017-T2/IND-5465). R.A. acknowledges the European Social Fund (ESF) and the Youth Employment Initiative (YEI) of the Madrid region through the PEJD-2019-PRE/IND-16755 grant