11 research outputs found

    Merotelic attachments and non-homologous end joining are the basis of chromosomal instability

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    Although the large majority of solid tumors show a combination of mitotic spindle defects and chromosomal instability, little is known about the mechanisms that govern the initial steps in tumorigenesis. The recent report of spindle-induced DNA damage provides evidence for a single mechanism responsible for the most prominent genetic defects in chromosomal instability. Spindle-induced DNA damage is brought about by uncorrected merotelic attachments, which cause kinetochore distortion, chromosome breakage at the centromere, and possible activation of DNA damage repair pathways. Although merotelic attachments are common early in mitosis, some escape detection by the kinetochore pathway. As a consequence, a proportion of merotelic attachments gives rise to chromosome breakage in normal cells and in carcinomas. An intrinsic chromosome segregation defect might thus form the basis of tumor initiation. We propose a hypothesis in which merotelic attachments and chromosome breakage establish a feedback loop that results in relaxation of the spindle checkpoint and suppression of anti-proliferative pathways, thereby promoting carcinogenesis

    Dido3-dependent HDAC6 targeting controls cilium size

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    En la superficie de muchos tipos de células los mamíferos podemos encontrar cilios, los cuales participan en multitud de procesos fisiológicos que van desde el crecimiento celular y el desarrollo hasta la percepción del ambiente en el que se encuentran. Su importancia se pone de manifiesto si tenemos en cuenta algunas enfermedades causadas por defectos en estos orgánulos: el hidrocéfalo, la anosmia (pérdida del olfato) o la retinitis pigmentaria. El grupo de investigación del Centro Nacional de Biotecnología del CSIC dirigido por Karel H.M. van Wely estudia las proteínas involucradas en la formación y en el desensamblaje de los cilios. Si bien se conoce desde hace tiempo su regulación asociada a la mitosis de la céllulas, en este laboratorio del CNB se ha encontrado un mecanismo que regula el tamaño de los cilios cuando la célula no se está dividiendo. Los experimentos que ha realizado en este laboratorio Ainhoa Sánchez de Diego, publicados en la revista Nature Communications, muestran que cuando las céllulas no están creciendo la distribución subcelular de la deacetilasa HDAC6 es esencial para controlar el tamaño de los cilios.Primary cilia are involved in a variety of physiological processes such as sensing of the environment, cell growth, and development. Numerous developmental disorders and pathological arise from defects in these organelles. Multiple proteins that promote formation and disassembly of the primary cilium have been identified, but little is known about the mechanisms that control steady state cilium size. Here, we show that Dido3-dependent targeting of HDAC6 is a key determinant of cilium size in growth-arrested cells. The amount of either protein negatively correlates with cilium size, Dido3 availability at the centrosome governs ciliary HDAC6 levels, and redistribution of the two proteins controls tubulin acetylation. In turn, basal body localization of Dido3 and HDAC6 depend on the actin network, previously shown to limit cilium size independent of the cell cycle. These results show that not only kinase-dependent activation of a deacetylase but also its subcellular distribution controls substrate selection.This work is financed by grants PS09/00572 (Fondo de Investigación en Salud) and BFU2009-08395E, (Ministerio de Economía y Competitividad) to KvW, and grants 2010/BMD2502 (Comunidad Autónoma de Madrid) and SAF2010-21205 (Ministerio de Economía y Competitividad) to CMA.Peer reviewe

    Challenges teaching work from disrupt the causes socioaffective development at school

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    El informe expone aquellas manifestaciones y experiencias que, en el marco de la pasantía, aparecieron como factores que impactan el campo social y emotivo de los estudiantes, generando, contrario a su florecimiento, su ocultamiento. Preguntas como ¿Qué emociones conoces? ¿Qué relación tienen las emociones con los otros? ¿Qué se siente en determinadas situaciones y con determinadas personas? ¿Qué importancia tiene conocer lo que siente el otro? ¿Por qué ocultar las emociones antes que expresarlas? Entre otras, son las preguntas que motivaron la escritura de este trabajo y que generaron nuestra reflexión como docentes.The report expose those events and experiences as part of the internship, they appeared as factors that impact the social and emotional field of students, generating contrary to its flowering, its concealment. Questions like, What emotions do you know? What is the relationship with the other emotions? How does you feel in certain situations and with certain people? How important is knowing what the other feels? Why hide the emotions rather than express them? Among others, are the questions that prompted the writing of this work and that generated our reflection as teachers

    Synaptonemal complex assembly and H3K4Me3 demethylation determine DIDO3 localization in meiosis

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    Synapsis of homologous chromosomes is a key meiotic event, mediated by a large proteinaceous structure termed the synaptonemal complex. Here we describe a role in meiosis for the murine Death inducer obliterator (Dido) gene. The Dido gene codes for three proteins that recognize trimethylated histone H3 lysine 4 through their aminoterminal PHD domain. DIDO3, the largest of the three isoforms, localizes to the central region of the synaptonemal complex in germ cells. DIDO3 follows the distribution of the central region protein SYCP1 in Sycp3-/- spermatocytes, which lack the axial elements of the synaptonemal complex. This indicates that synapsis is a requirement for DIDO3 incoporation. Interestingly, DIDO3 is missing from the synaptonemal complex in Atm mutant spermatocytes, which form synapses but show persistent trimethylation of histone H3 lysine 4. In order to further address a role of epigenetic modifications in DIDO3 localization, we made a mutant of the Dido gene that produces a truncated DIDO3 protein. This truncated protein, which lacks the histone-binding domain, is incorporated in the synaptonemal complex irrespective of histone trimethylation status. DIDO3 protein truncation in Dido mutant mice causes mild meiotic defects, visible as gaps in the synaptonemal complex, but allows for normal meiotic progression. Our results indicate that histone H3 lysine 4 demethylation modulates DIDO3 localization in meiosis, and suggest epigenetic regulation of the synaptonemal complex.Ministerio de Salud (FIS PI051965) Comunidad de Madrid (S-BIO-0189-2006, P-GEN-0166-2006) Ministerio de Ciencia (RyC004-1886)Peer reviewe

    Libro Rojo de Peces Dulceacuícolas de Colombia (2012)

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    En el marco del Plan Operativo Anual (2010 – 2011 - 2012) del Programa de Biología de la Conservación y Uso de la Biodiversidad del Instituto de Investigación de Recursos Biológicos Alexander von Humboldt, se llevó a cabo la actualización del Libro Rojo de peces dulceacuícolas de Colombia o proceso de evaluación del riesgo de extinción y evolución del estado de conservación de las especies de peces dulceacuícolas, como también es conocido. Esta iniciativa se llevó a cabo con el aval del Ministerio de Ambiente, Vivienda y Desarrollo Territorial – MAVT (hoy Ministerio de Ambiente y Desarrollo Sostenible – MADS) y la participación del Instituto de Ciencias Naturales de la Universidad Nacional de Colombia, WWF Colombia, y la Universidad de Manizales. En este proceso contribuyeron más de 50 investigadores, vinculados a unas 30 instituciones académicas, gubernamentales y no gubernamentales.Bogotá, D. C

    ENGIU: Encuentro Nacional de Grupos de Investigación de UNIMINUTO.

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    El desarrollo del prototipo para el sistema de detección de Mina Antipersona (MAP), inicia desde el semillero ADSSOF perteneciente al programa de Administración en Seguridad y Salud en el trabajo de la UNIMINUTO, se realiza a partir de un detector de metales que emite una señal audible, que el usuario puede interpretar como aviso de presencia de un objeto metálico, en este caso una MAP. La señal audible se interpreta como un dato, como ese dato no es perceptible a 5 metros de distancia, se implementa el transmisor de Frecuencia Modulada FM por la facilidad de modulación y la escogencia de frecuencia de transmisión de acuerdo con las normas y resolución del Ministerio de Comunicaciones; de manera que esta sea la plataforma base para enviar los datos obtenidos a una frecuencia establecida. La idea es que el ser humano no explore zonas peligrosas y buscar la forma de crear un sistema que permita eliminar ese riesgo, por otro lado, buscar la facilidad de uso de elementos ya disponibles en el mercado

    Make EU trade with Brazil sustainable

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    Brazil, home to one of the planet's last great forests, is currently in trade negotiations with its second largest trading partner, the European Union (EU). We urge the EU to seize this critical opportunity to ensure that Brazil protects human rights and the environment

    Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

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    IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes

    Clinical and genetic characteristics of late-onset Huntington's disease

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    Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P <.001). Overall motor and cognitive performance (P <.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P <.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P <.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P <.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients
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