55 research outputs found

    Greece\u27s Debt Crisis: Overview, Policy Responses, and Implications

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    The Atlantic Ocean at the last glacial maximum: 1. Objective mapping of the GLAMAP sea-surface conditions

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    Recent efforts of the German paleoceanographic community have resulted in a unique data set of reconstructed sea-surface temperature for the Atlantic Ocean during the Last Glacial Maximum, plus estimates for the extents of glacial sea ice. Unlike prior attempts, the contributing research groups based their data on a common definition of the Last Glacial Maximum chronozone and used the same modern reference data for calibrating the different transfer techniques. Furthermore, the number of processed sediment cores was vastly increased. Thus the new data is a significant advance not only with respect to quality, but also to quantity. We integrate these new data and provide monthly data sets of global sea-surface temperature and ice cover, objectively interpolated onto a regular 1°x1° grid, suitable for forcing or validating numerical ocean and atmosphere models. This set is compared to an existing subjective interpolation of the same base data, in part by employing an ocean circulation model. For the latter purpose, we reconstruct sea surface salinity from the new temperature data and the available oxygen isotope measurements

    The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

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    BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

    Guidelines for Genome-Scale Analysis of Biological Rhythms

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    Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

    Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

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