2,885 research outputs found

    A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK/PI3K induced malignant growth

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    Somatic mutations activating MAPK/PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumour based on somatic expression of oncogenes that activate MAPK/PI3K signalling in neural progenitor cells. HRASV12 was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho‑(p)ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component. Application of a 8-gene signature to human brain tumours establishes that YAP activation distinguishes between mesenchymal glioblastoma and low grade glioma in a wide TCGA sample set including gliomas and glioblastomas (GBMs). This suggests that the activation of YAP may be an important event in brain tumour development, promoting malignant versus benign brain lesions. Indeed, co-expression of dominant active YAP (YAPS5A) and HRASV12 abolishes the development of heterotopias and leads to the sole development of aggressive tumours. Thus, we have developed a model proving that neurodevelopmental disorders and brain tumours may originate from the same somatic mutations activating oncogenes and established that YAP activation is a hallmark of malignant brain tumours

    The Impact of Company Grade Officer Self-Sacrificial Behavior on Subordinate Assessments of Leader Charisma

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    Newly commissioned officers in the U.S. Army are taught to lead their soldiers from the front and to voluntarily make personal sacrifices in the service of the nation. Although this facet of military culture is seen as critical to the integrity of the force, there are few research studies describing the impact of leader self-sacrifice in the U.S. Army. Research evolving from the transformational leadership literature indicates that civilian leaders who engage in self-sacrificial behavior are viewed as more charismatic than their counterparts and that this perception is particularly pronounced in crisis situations. The current study extended this research to a military population utilizing a quantitative experimental research design. Respondents were randomly assigned to written vignettes that manipulated leader self-sacrifice and the combat environment and then provided assessments of the company grade officer\u27s attributed charisma. Currently serving enlisted and commissioned officers in the California Army National Guard (n = 218) took part in the research, and ANOVA test results indicated that both self-sacrifice and the experience of combat significantly increase perceptions of a company grade officer\u27s attributed charisma. No significant interaction was found between leader self-sacrifice and combat. This study indicated that the self-sacrificial leadership model may have broad applicability across organizations and provides strong support for the Army\u27s emphasis on selfless service. This research can spur positive social change by fostering a more aspirational form of leadership within the Army that builds the psychological resilience of soldiers and results in stronger teams

    Anthocyanin Hybrid Nanopigments from Pomegranate Waste: Colour, Thermomechanical Stability and Environmental Impact of Polyester-Based Bionanocomposites

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    In the present work, anthocyanin (ACN) hybrid nanopigments were synthetized by using a natural pomegranate dye (PD) and calcined hydrotalcite (HT) and montmorillonite (MMT) nanoclays. A wide colour gamut was obtained with MMT-based nanopigments ranging from reddish to bluish hues caused by structural transformations of ACNs at different pH values. However, a buffer effect was observed with HT obtaining samples a similar final colour regardless of the synthesis conditions. Nanopigments added with a biomordant extracted from pomegranate peels showed a different colour compared to the incorporation of a commercial mordant due to the intrinsic colouring properties of the pomegranate bioadditive. The developed nanopigments were incorporated at 7 wt% loading to produce novel polyester-based bionanocomposites which were characterized in terms of thermal, mechanical and colour properties. The encapsulation of PD into the nanoclays improved its thermal stability, in particular for MMT-based nanopigments. The pH changes observed during the nanofillers synthesis affected the final colour of the MMT-based nanocomposites, inducing a general increase in ∆E* and a decrease in gloss values. Slight improvements were obtained in terms of elastic modulus for MMT-based polymer samples confirming the applicability of the developed bionanocomposites as colouring and reinforcement materials. A very similar environmental profile was obtained for MMT and HT-based nanofillers showing MMT-based nanopigments a slightly better general behaviour. The results of the LCA study evidenced the suitability of the processes used in this work to the circular bioeconomy approach through sustainable food waste management and the production of bioplastics using waste substrates.This project has received funding from the Bio Based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 745578

    Rationally modified estrogen receptor protein as a bio-recognition element for the detection of EDC pollutants: strategies and opportunities

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    The estrogen receptor protein (ER) can bind a vast number of organic pollutants widely spread in the environment and collectively known as Endocrine Disrupting Chemicals, EDCs. Its broad selectivity makes it an ideal bio-recognition element for the detection of EDCs. Here we describe the strategy and rationale for the design of ER based biosensors and assays that generate a signal in the presence of EDCs. The opportunity to use either natural or rationally modified ER molecules is discussed. The latter approach was successfully applied in the EU-FP7 project RADAR, with the aim to develop a novel biosensor for the detection of organic pollutants both in the environment and in commercial water products

    VLTI status update: a decade of operations and beyond

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    We present the latest update of the European Southern Observatory's Very Large Telescope interferometer (VLTI). The operations of VLTI have greatly improved in the past years: reduction of the execution time; better offering of telescopes configurations; improvements on AMBER limiting magnitudes; study of polarization effects and control for single mode fibres; fringe tracking real time data, etc. We present some of these improvements and also quantify the operational improvements using a performance metric. We take the opportunity of the first decade of operations to reflect on the VLTI community which is analyzed quantitatively and qualitatively. Finally, we present briefly the preparatory work for the arrival of the second generation instruments GRAVITY and MATISSE.Comment: 10 pages, 7 figures, Proceedings of the SPIE, 9146-1

    Global Alliance for the Promotion of Physical Activity: the Hamburg Declaration

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    Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings

    Performance of LHC Main Dipoles for Beam Operation

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    At present about 90% of the main dipoles for the LHC have been manufactured and one of the three cold mass assemblers has already completed the production. 85% of the 1232 dipoles needed for the tunnel have been tested and accepted. In this paper we mainly deal with the performance results: the quench behaviour, the magnetic field quality, the electrical integrity quality and the geometry features will be summarized
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