295 research outputs found

    Soft Law and the International Law of the Environment

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    Because the existing body of international environmental law has, in part, emerged on the basis of soft norms, it provides a good field for observing the general sociological and juridical phenomenon termed soft law. The 1972 Stockholm Declaration adopted by the UN Conference on the Human Environment, for example, constitutes the normative program for the world community \u27in this field. Although, from a formal point of view, the Declaration is only a nonbinding resolution, many of its principles, particularly Principle 21, have been relied upon by governments to justify their legal rights and duties. The subsequent State practice has been, no doubt, influenced by such provisions. It is in this context and with the benefit of these introductory remarks that we shall briefly and successively examine the creation (I), the forms and content (II), and the legal effects (III) of soft law in the field of international environmental law

    Conclusiones del profesor Pierre-Marie Dupuy sobre el Derecho Internacional ante el siglo XXI

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    Sustainable Development and Integration

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    CHAPTER 4 - Sustainable Development and Integration: The principle of sustainable development is undeniably a cornerstone of international environmental law that has shaped the field since at least the 1980’s. Its most accepted definition is that of development that “meets the needs of the present without compromising the ability of future generations to meets their own needs”. Rooted in anthropocentrism, the notion originally stems from the realisation that environmental degradation and economic development are intimately linked and interdependent. It stems from the recognition that a sound environmental base is paramount for sustainable economic development (including the acknowledgment that environmental degradation fuels poverty) and that conversely patterns of development based principally on economic growth are no longer sustainable in view of the impairment of the sound environmental base they lead to. Despite legitimate criticism that the definition offered by the Brundtland Commission is too vague to ascertain sustainable development’s conceptual or legal content, it is generally accepted that sustainable development, following Rio+5 and the World Summit for Sustainable development, must be understood in terms of the reconciliation and mutual support between three interdependent pillars: economic development, environmental protection and social development. Crucially, such reconciliation and mutual support is to be achieved through a process of integration of these concerns. The principle of integration, formulated at principle 4 of the Rio Declaration which posits that “In order to achieve sustainable development, environmental protection shall constitute an integral part of the development process and cannot be considered in isolation from it”, thus represent the main means by which sustainable development is to be achieved

    Genetics of venous thrombosis: insights from a new genome wide association study

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    Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∌7% of the total genetic variance. Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT

    CD95 recruits PLCÎł1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice

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    CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L, and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase CÎł1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway may be attractive therapeutic approach for SLE treatment

    CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice

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    CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase CÎł1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment
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