1,136 research outputs found

    Causes and consequences of monodominance in tropical lowland forests

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    Journal ArticleTropical canopy dominance in lowland, well-drained forests by one plant species is a long-standing conundrum in tropical biology. Research now shows that dominance is not the result of one trait or mechanism. We suggest that the striking dominance of Gilbertiodendron dewevrei in the Ituri Forest of northeastern Congo is the result of a number of traits in adult trees that significantly modify the understory environment, making it difficult for other species to regenerate there

    Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils

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    A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that – despite the diverse array of genetic lesions typical of cancer – some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development

    Vesicular-arbuscular mycorrhizae in two tropical monodominant trees

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    Journal ArticleMycorrhizae, symbioses between plant roots and fungi, are found in virtually all terrestrial plant ecosystems. Substantial evidence indicates that mycorrhizal associations are beneficial to both partners

    Vesicular-arbuscular mycorrhizae in two tropical monodominant trees

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    Journal ArticleMycorrhizae, symbioses between plant roots and fungi, are in virtually all terrestrial plant ecosystems. Substantial evidence indicates that mycorrhizal associations are beneficial to both partners. In most systems, the fungus benefits the host plant by effectively scavenging nutrients and in return, utilizes carbohydrates produced by the plant (Allen 1991, Harley & Smith 1983)

    Analytic Considerations in Economic Evaluations of Multinational Cardiovascular Clinical Trials

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    OBJECTIVES: The growing number of economic evaluations that use data collected in multinational clinical trials raises numerous questions regarding their execution and interpretation. Although recommendations for conducting economic evaluations have been widely disseminated, relatively little guidance has been given for conducting economic evaluations alongside clinical trials, particularly multinational trials. METHODS: Building on a literature review that was conducted in preparation for an expert workshop, we evaluated a subset of methodological issues related to conducting economic evaluations alongside multinational clinical trials. RESULTS: We found wide variation in the types of costs included as part of the analyses and in the methods used to assign costs to hospitalization events. Furthermore, we found that the extrapolation of costs and survival outcomes beyond the trial period is an inconsistent practice and is often not dependent on whether a survival benefit was observed in the trial or on the epidemiology or practice patterns in the country to which the findings are directed. CONCLUSIONS: Although the limited sample size precluded a quantitative analysis of trial characteristics and their associations with the methodologies employed, our findings highlight the need for more guidance to analysts regarding the execution of economic evaluations using data from multinational clinical trials. As the research community grapples with the complexities of methodological and logistical issues involved in multinational economic evaluations, the development of a standardized format to report the basic methodological characteristics of such studies would help to improve transparency and comparability for other analysts and decision-makers

    Amyloid peptide β1-42 induces integrin αIIbβ3 activation, platelet adhesion and thrombus formation in a NADPH oxidase-dependent manner

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    This is the final version. Available on open access from Hindawi Publishing Corporation via the DOI in this recordThe progression of Alzheimer’s dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects of β amyloid peptides on the function of platelets, the cells driving haemostasis. Amyloid peptide β1-42 (Aβ1-42), Aβ1-40, and Aβ25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to Aβ1-42 compared to other Aβ peptides. In addition, significant platelet spreading was observed over Aβ1-42, while Aβ1-40, Aβ25-35, and the scAβ1-42 control did not seem to induce any platelet spreading, which suggested that only Aβ1-42 activates platelet signalling in our experimental conditions. Aβ1-42 also induced significant platelet adhesion and thrombus formation in whole blood under venous flow condition, while other Aβ peptides did not. The molecular mechanism of Aβ1-42 was investigated by flow cytometry, which revealed that this peptide induces a significant activation of integrin αIIbβ3, but does not induce platelet degranulation (as measured by P-selectin membrane translocation). Finally, Aβ1-42 treatment of human platelets led to detectable levels of protein kinase C (PKC) activation and tyrosine phosphorylation, which are hallmarks of platelet signalling. Interestingly, the NADPH oxidase (NOX) inhibitor VAS2870 completely abolished Aβ1-42-dependent platelet adhesion in static conditions, thrombus formation in physiological flow conditions, integrin αIIbβ3 activation, and tyrosine- and PKC-dependent platelet signalling. In summary, this study highlights the importance of NOXs in the activation of platelets in response to amyloid peptide β1-42. The molecular mechanisms described in this manuscript may play an important role in the neurovascular impairment observed in Alzheimer’s patients.Alzheimer´s Research UKBritish Heart FoundationNational Institute for Health Research (NIHR

    Amyloid peptide β 1-42 induces integrin α IIb β 3 activation, platelet adhesion, and thrombus formation in a NADPH Oxidase-Dependent Manner

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    The progression of Alzheimer's dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects of β amyloid peptides on the function of platelets, the cells driving haemostasis. Amyloid peptide β1-42 (Aβ1-42), Aβ1-40, and Aβ25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to Aβ1-42 compared to other Aβ peptides. In addition, significant platelet spreading was observed over Aβ1-42, while Aβ1-40, Aβ25-35, and the scAβ1-42 control did not seem to induce any platelet spreading, which suggested that only Aβ1-42 activates platelet signalling in our experimental conditions. Aβ1-42 also induced significant platelet adhesion and thrombus formation in whole blood under venous flow condition, while other Aβ peptides did not. The molecular mechanism of Aβ1-42 was investigated by flow cytometry, which revealed that this peptide induces a significant activation of integrin αIIbβ3, but does not induce platelet degranulation (as measured by P-selectin membrane translocation). Finally, Aβ1-42 treatment of human platelets led to detectable levels of protein kinase C (PKC) activation and tyrosine phosphorylation, which are hallmarks of platelet signalling. Interestingly, the NADPH oxidase (NOX) inhibitor VAS2870 completely abolished Aβ1-42-dependent platelet adhesion in static conditions, thrombus formation in physiological flow conditions, integrin αIIbβ3 activation, and tyrosine- and PKC-dependent platelet signalling. In summary, this study highlights the importance of NOXs in the activation of platelets in response to amyloid peptide β1-42. The molecular mechanisms described in this manuscript may play an important role in the neurovascular impairment observed in Alzheimer's patients

    Superconducting Rebalance Accelerometer

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    A multi-axis accelerometer which utilizes a magnetically-suspended, high-TC proof mass is under development. The design and performance of a single axis device which is stabilized actively in the axial direction but which utilizes ring magnets for passive radial stabilization is discussed. The design of a full six degree-of-freedom device version is also described
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