Open Data for Global Science

The global science system stands at a critical juncture. On the one hand, it is overwhelmed by a hidden avalanche of ephemeral bits that are central components of modern research and of the emerging ‘cyberinfrastructure’4 for e-Science.5 The rational management and exploitation of this cascade of digital assets offers boundless opportunities for research and applications. On the other hand, the ability to access and use this rising flood of data seems to lag behind, despite the rapidly growing capabilities of information and communication technologies (ICTs) to make much more effective use of those data. As long as the attention for data policies and data management by researchers, their organisations and their funders does not catch up with the rapidly changing research environment, the research policy and funding entities in many cases will perpetuate the systemic inefficiencies, and the resulting loss or underutilisation of valuable data resources derived from public investments. There is thus an urgent need for rationalised national strategies and more coherent international arrangements for sustainable access to public research data, both to data produced directly by government entities and to data generated in academic and not-for-profit institutions with public funding. In this chapter, we examine some of the implications of the ‘data driven’ research and possible ways to overcome existing barriers to accessibility of public research data. Our perspective is framed in the context of the predominantly publicly funded global science system. We begin by reviewing the growing role of digital data in research and outlining the roles of stakeholders in the research community in developing data access regimes. We then discuss the hidden costs of closed data systems, the benefits and limitations of openness as the default principle for data access, and the emerging open access models that are beginning to form digitally networked commons. We conclude by examining the rationale and requirements for developing overarching international principles from the top down, as well as flexible, common-use contractual templates from the bottom up, to establish data access regimes founded on a presumption of openness, with the goal of better capturing the benefits from the existing and future scientific data assets. The ‘Principles and Guidelines for Access to Research Data from Public Funding’ from the Organisation for Economic Cooperation and Development (OECD), reported on in another article by Pilat and Fukasaku,6 are the most important recent example of the high-level (inter)governmental approach. The common-use licenses promoted by the Science Commons are a leading example of flexible arrangements originating within the community. Finally, we should emphasise that we focus almost exclusively on the policy—the institutional, socioeconomic, and legal aspects of data access—rather than on the technical and management practicalities that are also important, but beyond the scope of this article

IGF and IGF-binding protein system in the synovial fluid of osteoarthritic and rheumatoid arthritic patients.

International audienceVarious arthritic disorders result from a disruption of the equilibrium between the synthesis and degradation of tissue matrix macromolecules. Growth factors, particularly insulin-like growth factor-I (IGF-I), are believed to play an important role in maintaining this equilibrium. In this study, we determined the levels of IGF-I, IGF-II, and characterized and measured the amount of IGF-binding proteins (IGFBPs) in the synovial fluid (SF) of osteoarthritis (OA), rheumatoid arthritis (RA) patients and normal individuals. Furthermore, we characterized the IGFBP found in these SFs. The levels of IGF-I, IGF-II and IGFBP-3 were determined by specific radioimmunoassays (RIAs). IGFBP identification and measurement were carried out using the Western ligand blot (WLB) technique, and characterization performed by Western immunoblot. IGFBP-3 proteolysis was analyzed by autoradiography after incubation of SF with radiolabeled IGFBP-3. Results showed a statistically significant increase (P < 0.001) in the IGF-I level in arthritic SF vs normal controls; 75 +/- 11 ng/ml and 82 +/- 11 ng/ml were recorded for RA (N = 8) and OA (N = 10), respectively, whilst normal controls (N = 9) were at 19 +/- 7 ng/ml. No difference in the level of IGF-II was recorded between the three groups studied. Human SF demonstrated the presence of IGFBP-1, -2, -3 and -4, but not that of IGFBP-5 and -6. The level of IGFBP-3 tested either by WLB or RIA was significantly higher (P < 0.001) in RA and OA patients. Moreover, a statistical and positive correlation between the levels of IGF-I and IGFBP-3 was noted. WLB analysis indicated that the amount of IGFBP-1 did not vary among the groups. The levels of IGFBP-2 and -4 were significantly increased (P < 0.02) solely in the RA SF. Further experiments demonstrated that a limited IGFBP-3 proteolysis occurred in human SF. Moreover, the ratio of total IGF over total bioactive IGFBPs was lower in RA (P < 0.05), and to a lesser extent in OA than normal specimens. This study showed the presence of four IGFBPs (1 4) in human SF for which the IGFBP-2, -3 and -4 were enhanced in arthritic fluid. Importantly, although proteolysis occurred in the SF, an increased amount of bioactive IGFBPs were present in arthritic SF, which may affect the bioavailability of IGF-I within the articular tissues

The acylated (AG) to unacylated (UAG) ghrelin ratio in esterase inhibitor-treated blood is higher than previously described

ContextThe acylated/unacylated ghrelin (AG/UAG) ratio has been reported to range from 002 to 03, suggesting biologically relevant independent regulation of each ghrelin isoform. However, AG is deacylated to UAG by esterases in blood samples, and esterase inhibition is critical for their accurate measurement. Our hypothesis is that at least part of the variation in reported AG and UAG values is due to inconsistent sample preparation. DesignA non-interventional study. Quantification with two different, commercially available, ELISA formats of AG and UAG in venous plasma stabilized or not with 4-(2-aminoethyl) benzenesulphonyl fluoride (AEBSF) and stored for 0-6months at -20 or -80 degrees C. ParticipantsHealthy, non-obese, adults (n=8; 4 women), age 26-42yrs, after an overnight fast. MeasurementsAG and UAG stability following different methods of sample treatment and storage. ResultsNon-AEBSF plasma contained low AG and high UAG (>270pg/ml) indicating rapid conversion of AG to UAG. However, AEBSF plasma, stored at -80 degrees C and measured at 0, 1, 3 and 6months contained AG and UAG ranges of 12-350 and 17-170pg/ml, respectively. Mean (SEM) AG/UAG ratios were 17(03), 12(02), 15(03) and 18(05) at each time point with no significant effect of storage period. ConclusionsAG and UAG levels measured in AEBSF-stabilized plasma indicate that the AG/UAG ratio is markedly higher than previously described and that UAG is a physiological component of the circulation. This highlights the importance of immediately stabilizing blood samples on collection for determination of both AG and UAG concentrations and provides a valuable tool for their measurement in physiological and interventional studies

Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans.

Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). UAG, however, is not biologically inactive; it shares with AG some non-endocrine actions like cardiovascular effects, modulation of cell proliferation and even some influence on adipogenesis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 microg/kg i.v.) in 6 normal young volunteers (age [mean +/- SE]: 25.4 +/- 1.2 yr; BMI: 22.3 +/- 1.0 kg/m2). As expected, AG induced marked increase (p < 0.01) in circulating GH, PRL, ACTH and cortisol levels. AG administration was also followed by a decrease in insulin levels (-285.4 +/- 64.8 mU*min/l; p < 0.05) and an increase in plasma glucose levels (1068.4 +/- 390.4 mg*min/dl; p < 0.01). UAG alone did not induce any change in these parameters. UAG also failed to modify the GH, PRL, ACTH and cortisol responses to AG. However, when UAG was co-administered together with AG, no significant change in insulin (-0.5 +/- 40.9 mU*min/l) and glucose levels (455.9 +/- 88.3 mg*min/dl) was recorded anymore, indicating that the insulin and glucose response to AG has been abolished by UAG. In conclusion, non-acylated ghrelin does not affect the GH, PRL, and ACTH response to acylated ghrelin but is able to antagonize the effects of acylated ghrelin on insulin secretion and glucose levels. These findings indicate that unacylated ghrelin is metabolically active and is likely to counterbalance the influence of acylated ghrelin on insulin secretion and glucose metabolism. As GHS-R1a is not bound by unacylated ghrelin, these findings suggest that GHS receptor subtypes mediate the metabolic actions of both acylated and unacylated ghrelin

The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans

Context: Acylated ghrelin (AG) has been discovered as a natural ligand of the GH secretagogue receptor type 1 a and is now recognized as an important orexigenic factor. Besides stimulation of GH secretion and appetite, it exerts other central and peripheral actions including modulation of insulin secretion, glucose and lipid metabolism. Objective: To define the effects of the continuous iv infusion of AG in humans with particular attention to metabolic parameters. Materials and methods: We studied the effects of 16h (from 21:00 to 13:00 h) infusion of AG (0.5 mu g/kg/h) or saline in 8 young volunteers who were provided with isocaloric balanced meals. GH, cortisol, insulin, glucose, free fatty acid (FFA), and ghrelin levels were assayed every 20 min. Results: AG infusion increased circulating total ghrelin to a steady state that was maintained over 16 h infusion of the peptide. With respect to saline, AG infusion significantly modified GH, cortisol, insulin, and glucose profiles and decreased FIFA area under the curve (p<0.01). AG increased GH pulse frequency and approximate entropy (p<0.05). AG enhanced the glucose response to both dinner (p<0.02) and breakfast (p<0.03). AG infusion blunted the early insulin response to dinner (p<0.03) but enhanced the second-phase insulin response to dinner and breakfast (p<0.05). Conclusions: The continuous exposure to AG in humans enhances somatotroph secretion but also worsens glucose metabolism, although it inhibits lipolysis. These findings in normal young volunteers are consistent with data from studies in animals and suggest that acylated ghrelin is likely to play a negative role in glucose metabolism

The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans.

CONTEXT: Acylated ghrelin (AG) has been discovered as a natural ligand of the GH secretagogue receptor type 1a and is now recognized as an important orexigenic factor. Besides stimulation of GH secretion and appetite, it exerts other central and peripheral actions including modulation of insulin secretion, glucose and lipid metabolism. OBJECTIVE: To define the effects of the continuous iv infusion of AG in humans with particular attention to metabolic parameters. MATERIALS AND METHODS: We studied the effects of 16- h (from 21:00 to 13:00 h) infusion of AG (0.5 microg/kg/h) or saline in 8 young volunteers who were provided with isocaloric balanced meals. GH, cortisol, insulin, glucose, free fatty acid (FFA), and ghrelin levels were assayed every 20 min. RESULTS: AG infusion increased circulating total ghrelin to a steady state that was maintained over 16 h infusion of the peptide. With respect to saline, AG infusion significantly modified GH, cortisol, insulin, and glucose profiles and decreased FFA area under the curve (p<0.01). AG increased GH pulse frequency and approximate entropy (p<0.05). AG enhanced the glucose response to both dinner (p<0.02) and breakfast (p<0.03). AG infusion blunted the early insulin response to dinner (p<0.03) but enhanced the second-phase insulin response to dinner and breakfast (p<0.05). CONCLUSIONS: The continuous exposure to AG in humans enhances somatotroph secretion but also worsens glucose metabolism, although it inhibits lipolysis. These findings in normal young volunteers are consistent with data from studies in animals and suggest that acylated ghrelin is likely to play a negative role in glucose metabolism