2,723 research outputs found

    Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation

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    This work was supported by grants from the Wellcome Trust/Royal Soci‑ ety (101225/Z/13/Z) and MRC (MR/X008487/1) to M.R.B.; and BBSRC (BB/ T000031/1) to M.R.B. and J.M.F.Background Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.Wellcome Trust/Royal Society (101225/Z/13/Z)MRC (MR/X008487/1)BBSRC (BB/T000031/1

    Microalga marina y su empleo en acuicultura y en la obtención de ácidos grasos poliinsaturados

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    Número de publicación: ES2088366 A1 (01.08.1996) También publicado como: ES2088366 B1 (01.03.1997) Número de Solicitud: Consulta de Expedientes OEPM (C.E.O.) P9500053 (13.01.1995)Una cepa de la microalga marina isochrysis galbana, depositada en la CCAP con el número de depósito CCAP 927/15 es capaz de producir elevadas cantidades de ácidos grasos poliinsaturados, especialmente de ácido eicosapentaenoico (EPA) y de ácido docosahexaenoico (DHA). La cepa microalgal crece adecuadamente a una temperatura de 18 c a 25 c, en un ph de 7 a 9,5, preferentemente a un ph de 7,65 a 8,00. La cepa microalgal, cultivada a 20 c en un fermentador de 5 litros agitado por paletas y con iluminación continua, produce EPA en una cantidad de, al menos, 39,5 mg por gramo de materia seca. Esta cepa es adecuada para su empleo en acuicultura (alimentación de larvas de peces y moluscos) y en la obtención de EPA y/o de un aceite rico en EPA y en DHA necesarios para la nutrición y salud humanas.Universidad de Almerí

    Business computing - A shared curriculum proposal for the spanish-portuguese border under the auspices of the new european higher education area

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    The Bologna Declaration is leading to a change of paradigm in the context of higher education in many countries of the European Community; it has a significant impact at the level of curriculum and learning models. Therefore, any reflection and decision work on the processes of teaching/learning imposes the curricular reformulation of higher courses in an innovating way, supported by new references and assumptions. In the context of a project financed by European Community program Interreg III A, we have created a workgroup to o propose the reformulation of several courses that belong to Business Computing, from ESTiG-Portugal and from ESPZ-Spain, in an attempt to create harmony between both study plans, considering the socio-economic specific context of the border region between Braganca (Portugal) and Zamora (Spain). This article intends to describe a case-study related to the work done to achieve a curriculum for Business Computing; it describes the changes due to the recent recommendations of Bologna and governmental reflections of Portugal and Spain.This study was partly financed by the European Union with INTERREG III A funds

    Cochleates derived from Vibrio cholerae O1 proteoliposomes : The impact of structure transformation on mucosal immunisation

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    Cochleates are phospholipid-calcium precipitates derived from the interaction of anionic lipid vesicles with divalent cations. Proteoliposomes from bacteria may also be used as a source of negatively charged components, to induce calcium-cochleate formation. In this study, proteoliposomes from V. cholerae O1 (PLc) (sized 160.7±1.6 nm) were transformed into larger (16.3±4.6 µm) cochleate-like structures (named Adjuvant Finlay Cochleate 2, AFCo2) and evaluated by electron microscopy (EM). Measurements from transmission EM (TEM) showed the structures had a similar size to that previously reported using light microscopy, while observations from scanning electron microscopy (SEM) indicated that the structures were multilayered and of cochleate-like formation. The edges of the AFCo2 structures appeared to have spaces that allowed penetration of negative stain or Ovalbumin labeled with Texas Red (OVA-TR) observed by epi-fluorescence microscopy. In addition, freeze fracture electron microscopy confirmed that the AFCo2 structures consisted of multiple overlapping layers, which corresponds to previous descriptions of cochleates. TEM also showed that small vesicles co-existed with the larger cochleate structures, and in vitro treatment with a calcium chelator caused the AFCo2 to unfold and reassemble into small proteoliposome-like structures. Using OVA as a model antigen, we demonstrated the potential loading capacity of a heterologous antigen and in vivo studies showed that with simple admixing and administration via intragastric and intranasal routes AFCo2 provided enhanced adjuvant properties compared with PLc

    La laminoartrectomía en el tratamiento de la estenosis de canal lumbar

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    Los autores presentan una revisión de 42 pacientes, 33 varones y 9 mujeres, con estenosis del canal lumbar, tratados quirúrgicamente y con un seguimiento medio de 3 años y 8 meses. El tratamiento quirúrgico empleado ha sido la laminoartrectomía a uno o varios niveles, combinada o no con artrodesis. Los mejores resultados se obtuvieron en los pacientes tratados con laminoartrectomía, artrodesis e instrumentación vertebral.The authors present a review of 42 patients, 33 male and 9 female, with lumbar spinal canal stenosis, treated surgically and with a mean follow-up of 3 years-8 months. The surgical treatment was wide laminoarthrectomy involving one o more levels, combined in some cases with spinal fusion. The best results were obtained in patients treated with laminoarthrectomy, arthrodesis and vertebral instrumentation

    Leptin and Gestational Diabetes Mellitus

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    Emerging research has highlighted the importance of leptin in fetal growth and development, independent of its essential role in the regulation of feeding and energy metabolism. Leptin is now considered an important signaling molecule of the reproductive system, since it regulates the production of gonadotropins, the blastocyst formation and implantation, the normal placentation, as well as the feto-placental communication. Placental leptin is an important cytokine which regulates placental functions in an autocrine or paracrine manner. Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes like proliferation, protein synthesis, invasion, and apoptosis in placental cells. Furthermore, deregulation of leptin levels has been correlated with the pathogenesis of various disorders associated with reproduction and gestation, including gestational diabetes mellitus (GDM). Due to the relevant incidence of the GDM and the importance of leptin, we decided to review the latest information available about leptin action in normal and GDM pregnancies to support the idea of leptin as an important factor and/or predictor of diverse disorders associated with reproduction and pregnancy

    Selection of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients Through the Identification of T-Cells Capable to Establish Stable Interactions With the Leukemic Cells: “Doublet Technology”

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    The relevance of the immune system in cancer has long been studied. Autologous adoptive T cell therapies, based on the use of tumor infiltrating lymphocytes (TILs), have made great progress in recent years for the treatment of solid tumors, especially melanoma. However, further work is needed to isolate tumor-reactive T cells among patients diagnosed with hematologic malignancies. The dynamics of the interaction between T cells and antigen presenting cells (APC) dictate the quality of the immune responses. While stable joints between target cells and T lymphocytes lead to the induction of T cell activation and immune response, brief contacts contribute to the induction of immune-tolerance. Taking advantage of the strong interaction between target cell and activated T-cells, we show the feasibility to identify and isolate tumor-specific cytotoxic T lymphocytes (CTLs) from acute myeloid leukemia (AML) patients by flow cytometry. Using this technology, CTLs bound through T cell receptor (TCR) to tumor cells can be identified in peripheral blood and bone marrow and subsequently selected and isolated by FACS-based cell sorting. These CTLs display higher percentage of effector cells and marked cytotoxic activity against AML blasts. In conclusion, we have developed a new procedure to identify and select specific cytotoxic T cells in patients diagnosed with acute myeloid leukemia.Instituto de Salud Carlos III PFIS-FI12/00189Instituto de Salud Carlos III ISCIII PI14/02074Instituto de Salud Carlos III PI11/02366Instituto de Salud Carlos III PI17/02177European Union (ERDF/ESF, Investing in your future)CIBER CB16/12/0048

    Distributed Real-Time Computation of the Point of Gaze

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    This paper presents a minimally intrusive real-time gaze-tracking prototype to be used in several scenarios, including a laboratory stall and an in-vehicle system. The system requires specific infrared illumination to allow it to work with variable light conditions. However, it is minimally intrusive due to the use of a carefully configured switched infrared LED array. Although the perceived level of illumination generated by this array is high, it is achieved using low-emission infrared light beams. Accuracy is achieved through a precise estimate of the center of the user's pupil. To overcome inherent time restrictions while using low-cost processors, its main image-processing algorithm has been distributed over four main computing tasks. This structure not only enables good performance, but also simplifies the task of experimenting with alternative computationally-complex algorithms and with alternative tracking models based on locating both user eyes and several cameras to improve user mobility

    A Performance/Cost Model for a CUDA Drug Discovery Application on Physical and Public Cloud Infrastructures

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    Virtual Screening (VS) methods can considerably aid drug discovery research, predicting how ligands interact with drug targets. BINDSURF is an efficient and fast blind VS methodology for the determination of protein binding sites, depending on the ligand, using the massively parallel architecture of graphics processing units(GPUs) for fast unbiased prescreening of large ligand databases. In this contribution, we provide a performance/cost model for the execution of this application on both local system and public cloud infrastructures. With our model, it is possible to determine which is the best infrastructure to use in terms of execution time and costs for any given problem to be solved by BINDSURF. Conclusions obtained from our study can be extrapolated to other GPU‐based VS methodologiesIngeniería, Industria y Construcció
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