Misappropriation of Shuar Traditional Knowledge (TK) and Trade Secrets: A Case Study on Biopiracy in the Amazon

Where the murkiness of biopiracy as a general matter leaves little room for legal theory to anchor, the relative clarity of specific instances of biopiracy may provide sufficient factual information from which to develop appropriate legal theories. In particular, the way biopiracy has been used to misappropriate the traditional knowledge (TK) of the Shuar Nation of Ecuador suggests that there may be legal theories for which the process of misappropriation may give rise to liability under international law as well as under developments in the domestic laws of the United States and Ecuador. The possible efficacy and legal coherence of any such theory are dependent upon an understanding of the background of the problem of biopiracy, the general and specific methods used by biopirates, and a clarification of the nature of the interests in question as misappropriated property. Part II of this Article provides an outline of the importance of biodiversity and TK for medical and pharmaceutical interests and develops a generic model of bioprospecting, which has been used as a cover for acts of biopiracy. The model is drawn from general experience as well as the specific facts in our possession. This section then details how the bioprospecting and biopiracy process actually works in practice, including an outline of the operations of biopiracy in the specific case of the Shuar. Part III raises the proposition-widely accepted as conventional wisdom-that indigenous societies have no legally recognizable concept of property and a fortiori cannot have a notion of TK as a property value. This section then addresses the ensuing question of whether TK has the requisite qualities to be considered protectable property at all, and proposes the central principle that indigenous people indeed have concepts of property well recognized in contemporary analytical jurisprudence. Moreover, this section suggests that these same insights are firmly established in legal anthropology as well as in conventional jurisprudence. Finally, the section deals specifically with TK as property, contained within the secretive Shaman tradition of the Amazon Rain Forest, recognizing that it is because the Shaman TK was held to be a secret in the first place that bioprospecters have used extraordinary means of deception to misappropriate such knowledge. Part IV explores the concept of TK in the context of the development of such ideas as the “new property,” which includes, in particular, intellectual property, providing an appraisal of the problems of protecting TK against the ideological assumptions and misconceptions of certain aspects of intellectual property law. This Article concludes by proposing that the concept of property under the Inter-American system may well include TK as property for the purpose of protecting such property under the Inter-American Convention

Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in Ophthalmic Neoangiogenesis Models

Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema. Accordingly, drugs targeting VEGF are becoming mainstream treatments for these diseases. The crosstalk between leptin and VEGF has been noted in different tissues, but its involvement in the development of eye pathologies is unclear. Leptin is coexpressed with VEGF during ocular neovascularization and can potentiate VEGF synthesis and angiogenic function. However, whether or not VEGF regulates leptin expression or signaling has never been studied. Consequently, we addressed this aspect of leptin/VEGF crosstalk in ocular models, focusing on therapeutic exploration of underlying mechanisms.Here we show, for the first time, that in retinal (RF/6A) and corneal (BCE) endothelial cells, VEGF (100 ng/mL, 24 h) stimulated leptin mRNA synthesis by 70 and 30%, respectively, and protein expression by 56 and 28%, respectively. In parallel, VEGF induced RF/6A and BCE cell growth by 33 and 20%, respectively. In addition, VEGF upregulated chemotaxis and chemokinesis in retinal cells by ~40%. VEGF-dependent proliferation and migration were significantly reduced in the presence of the leptin receptor antagonist, Allo-aca, at 100-250 nmol/L concentrations. Furthermore, Allo-aca suppressed VEGF-dependent long-term (24 h), but not acute (15 min) stimulation of the Akt and ERK1/2 signaling pathways. The efficacy of Allo-aca was validated in the rat laser-induced choroidal neovascularization model where the compound (5 μg/eye) significantly reduced pathological vascularization with the efficacy similar to that of a standard treatment (anti-VEGF antibody, 1 μg/eye).Cumulatively, our results suggest that chronic exposure to VEGF upregulates leptin expression and function. As leptin can in turn activate VEGF, the increased abundance of both cytokines could amplify pro-angiogenic and pro-inflammatory environement in the eye. Thus, combined therapies targeting ObR and VEGF should be considered in the treatment of ocular diseases

Towards Independent Particle Reconstruction from Cryogenic Transmission Electron Microscopy

Coronary heart disease is the single largest killer of Americans so improved means of detecting risk factors before arterial obstructions appear are expected to lead to a improvement in quality of life with a reduced cost. This paper introduces a new approach to 3-D reconstruction of individual particles based on statistical modeling from a sparse set of 2-D projection images. This paper introduces a new approach to 3-D reconstruction of individual particles based on statistical modeling from a sparse set of 2-D projection images. The method is in contrast to the current state of practice where reconstruction is performed via signal processing or Bayesian methods that use averaged images acquired from an ensemble of particles. As such, this new approach has its impetus in use for novel diagnostic tests such as LDL and HDL particle shape characterization. The approach is also expected to have uses in areas such as quality assurance for drug delivery nano-technologies and for general proteomic studies. The individual particle reconstruction algorithm is based on a hidden Markov model. Higher order Markov chain statistics, which are generated from the a priori model of the target of interest, can be derived from traditional methods such as single particle reconstruction and/or the underlying physical properties of the particle. By placing the reconstruction voxel space at a 45° angle to the projection image, 4-passes of the HMM processing can be performed from a single image. Reconstruction results from a simple model and a single projection image resulted in better than 98% reconstruction accuracy as compared to the original target

Primary structure and spectroscopic studies of Neurospora copper metallothionein.

When Neurospora crassa is grown in the presence of Cu(II) ions, it accumulates the metal with the concomitant synthesis of a low molecular weight copper-binding protein. The molecule binds 6 g-atom of copper per mole protein (Mr = 2200) and shows a striking sequence homology to the zinc- and cadmium-binding vertebrate metallothioneins. Absorption, circular dichroism, and electron paramagnetic resonance spectroscopy of Neurospora metallothionein indicate the copper to be bound to cysteinyl residues as a Cu(I)-thiolate complex of the polymeric mu-thiolate structure [Cu(I)6RS7]-. This metal-binding mode is also in agreement with the unusual luminescence of the protein. Spectral perturbation studies with HgCl2 and p-(chloromercuri)benzoate suggest that the 6 Cu(I)ions are coordinated to the seven cysteinyl residues in the form of a single metal cluster. Neurospora apometallothionein is also capable of binding in vivo group IIB metal ions [Zn(II), Cd(II), and Hg(II)] as well as paramagnetic Co(II) ions with an overall metal-to-protein stoichiometry of 3. The spectroscopic properties of the fully substituted forms are indicative of a distorted tetrahedral coordination. However, metal titration of the apoprotein shows the third metal ion to be differently coordinated than the other two metal ions. This difference can be explained by the presence of only seven cysteine residues in Neurospora metallothionein as opposed to nine cysteine residues in the three-metal cluster of the mammalian metallothioneins

High Plasma Branched-Chain Amino Acids Are Associated with Higher Risk of Post-Transplant Diabetes Mellitus in Renal Transplant Recipients

Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (>= 18 y) with a functioning graft for >= 1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 +/- 13.6 y (53.6% men) and plasma BCAA was 377.6 +/- 82.5 mu M. During median follow-up of 5.3 (IQR, 4.2-6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08-1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c <5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM