Academic Responsibilities and Representation of the Ok Tedi Crisis in Postcolonial Papua New Guinea

Since the start of the Ok Tedi mining project in Papua New Guinea in 1981, Broken Hill Proprietary has operated it. Weak environmental protection laws and a series of ecological disasters have endangered the greater Ok Tedi and Fly River socioecological region. A grassroots indigenous popular ecological resistance movement made an out-of-court settlement with the mining company in Melbourne in 1996. Early in 2000 the indigenous movement took Broken Hill Proprietary back to court in Melbourne to block the company’s attempt to abandon the Ok Tedi mine. Research started with Wopkaimin subsistence ecology in the 1970s. Later the political ecology of the Ok Tedi crisis was evaluated, as was ecological change in social terms; both are illustrated through the politics of cultural and ecological representation. After the successful convergence of radical environmentalists and indigenous popular ecological resistance against the Ok Tedi mine, research shifted to liberation ecology to study the emancipatory potential of struggles and conflicts against environmental degradation. The responsibilities of academics conducting research in the Ok Tedi crisis are examined. The Ok Tedi crisis challenges the proposition that academics can act as honest bro k e r s t h rough mining companies to negotiate deals for local communities. Academics engaged by mining companies as consultants or employees must work according to managed science and circumscribed briefs. The approach of critical liberation ecology, which directs research to community empowerment, represents a freedom of critical inquiry only available in the academy

Changing relations of production in the creation of the Ok Tedi Mining enclave in Papua New Guinea

The interplay of mining, miners and indigenous peoples increasingly threatens the interdependence of cultural and biological diversity in Papua New Guinea. The mode of production concept provides anthropology with a useful theoretical tool for examining the survival of communities based on subsistence and simple reproduction. Mining characteristically transforms the cultural appropriation of nature and social relations of production among indigenous peoples. The survival of a community and their environment in the face of a mining project is conditioned by its production logic combined with relevant cultural and ecological particularities. The analytical significance of the mode of production concept is illustrated with a case study of Wopkaimin and their changing relations of production during the creation of the Ok Tedi mining project in the 1980’s

Elimination of the reaction rate 'scale effect': application of the Lagrangian reactive particle-tracking method to simulate mixing-limited, field-scale biodegradation at the Schoolcraft (MI, USA) site

This is the peer reviewed version of the following article: [Ding, D., Benson, D. A., Fernàndez‐Garcia, D., Henri, C. V., Hyndman, D. W., Phanikumar, M. S., & Bolster, D. (2017). Elimination of the reaction rate “scale effect”: Application of the Lagrangian reactive particle‐tracking method to simulate mixing‐limited, field‐scale biodegradation at the Schoolcraft (MI, USA) site. Water Resources Research, 53, 10,411–10,432. https://doi.org/10.1002/2017WR021103], which has been published in final form at https://doi.org/10.1002/2017WR021103. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Measured (or empirically fitted) reaction rates at groundwater remediation sites are typically much lower than those found in the same material at the batch or laboratory scale. The reduced rates are commonly attributed to poorer mixing at the larger scales. A variety of methods have been proposed to account for this scaling effect in reactive transport. In this study, we use the Lagrangian particle-tracking and reaction (PTR) method to simulate a field bioremediation experiment at the Schoolcraft, MI site. A denitrifying bacterium, Pseudomonas Stutzeri strain KC (KC), was injected to the aquifer, along with sufficient substrate, to degrade the contaminant, carbon tetrachloride (CT), under anaerobic conditions. The PTR method simulates chemical reactions through probabilistic rules of particle collisions, interactions, and transformations to address the scale effect (lower apparent reaction rates for each level of upscaling, from batch to column to field scale). In contrast to a prior Eulerian reaction model, the PTR method is able to match the field-scale experiment using the rate coefficients obtained from batch experiments.Peer ReviewedPostprint (author's final draft

Shifting Ecological Imaginaries in the Ok Tedi Mining Crisis in Papua New Guinea

Jusqu’à la fin des années soixante-dix, les systèmes de gestion de l’environnement par les propriétaires terriens de la haute rivière Ok Tedi en Papouasie Nouvelle- Guinée reposaient sur les possibilités d’accès et le contrôle des terres, des ressources et de l’eau. L’écologie de subsistance des années soixante-dix a fourni les éléments d’analyse des savoirs traditionnels concernant l’environnement et les droits et usages des ressources. Le projet minier d’Ok Tedi a vu le jour au début des années quatre-vingt. La mine est un projet à visée globale et les voies d’eau ont été soumises à rude épreuve au profit d’une gestion de l’environnement capitaliste et industrielle. Les propriétaires terriens de la région, vivant en économie d’autosubsistance à la périphérie de l’espace global, ont subi les affres de la transition complexe au capitalisme, face à des paysages ravagés par l’industrialisation ; pour eux, ce fut une expérience tout à fait nouvelle. L’écologie politique des années quatre-vingt a permis l’analyse de l’appropriation des ressources et de leur utilisation dans un système de production capitaliste. L’écologie immorale de la mine a menacé l’écologie morale de subsistance et s’est jouée entre une vision globale versus locale des imaginaires de l’environnement équipés de différents pouvoirs et technologies. L’écologie de libération des années quatre-vingt-dix nous renseigne sur les analyses du potentiel libératoire d’un mouvement de résistance écologique populaire apparu en réponse aux sévères dégradations de l’environnement dues à la mine et qui menacent les moyens d’existence de plus de 30 000 personnes vivant le long des rivières Ok Tedi et Fly. Aujourd’hui encore, cette crise minière, est caractérisée par des représentations conflictuelles de l’environnement entre mineurs, propriétaires terriens et chercheurs en sciences sociales.Until the end of the 1970s, landowner systems of environmental management in the upper Ok Tedi River in Papua New Guinea were based on local access to and control over land, water and resources. Subsistence ecology in the 1970s informed the analysis of customary ecological knowledge and resource use and rights. The Ok Tedi mining project started in the early 1980s. The mine is global in scope and its harsh treatment of the river systems set aside for production is common to capitalist industrial environmental management. For local subsistence-oriented landowners at the periphery of global space, being in the throes of complex capitalist transition and destroyed industrial landscape was an alien experience. Political ecology in the 1980s informed analysis of resource appropriation and commoditisation into capitalist relations of production. The immoral ecology of the mine threatened the moral ecology of subsistence and was played out in global-local articulations between environmental imaginaries armed with different powers and technologies. Liberation ecology in the 1990s informed the analysis of the libratory potential of a popular ecological resistance movement that emerged in response to severe environmental degradation from the mine that threatened the livelihood of over 30,000  people along the Ok Tedi and Fly Rivers. Representations of the Ok Tedi mining crisis continue to be characterised by conflicting environmental imaginaries between miners, landowners and social scientists

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

Introduction to Special Section: The Quest for Sustainability of Heavily Stressed Aquifers at Regional to Global Scales

This is the peer reviewed version of the following article: Butler, J. J., Gomez-Hernandez, J. J., Perrone, D., & Hyndman, D. (2021). Introduction to special section: The quest for sustainability of heavily stressed aquifers at regional to global scales. Water Resources Research, 57, e2021WR030446, which has been published in final form at https://doi.org/10.1029/2021WR030446. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The authors acknowledge financial support from the United States National Science Foundation (NSF), via grant EAR 1542320, to organize the Chapman meeting. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF.Butler Jr., JJ.; Gómez-Hernández, JJ.; Perrone, D.; Hyndman, DW. (2021). Introduction to Special Section: The Quest for Sustainability of Heavily Stressed Aquifers at Regional to Global Scales. Water Resources Research. 57(8):1-4. https://doi.org/10.1029/2021WR030446S1457

Endothelin.

The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action. Highly selective peptide ETA and ETB antagonists and ETB agonists together with radiolabeled analogs have accurately delineated endothelin pharmacology in humans and animal models, although surprisingly no ETA agonist has been discovered. ET antagonists (bosentan, ambrisentan) have revolutionized the treatment of pulmonary arterial hypertension, with the next generation of antagonists exhibiting improved efficacy (macitentan). Clinical trials continue to explore new applications, particularly in renal failure and for reducing proteinuria in diabetic nephropathy. Translational studies suggest a potential benefit of ETB agonists in chemotherapy and neuroprotection. However, demonstrating clinical efficacy of combined inhibitors of the endothelin converting enzyme and neutral endopeptidase has proved elusive. Over 28 genetic modifications have been made to the ET system in mice through global or cell-specific knockouts, knock ins, or alterations in gene expression of endothelin ligands or their target receptors. These studies have identified key roles for the endothelin isoforms and new therapeutic targets in development, fluid-electrolyte homeostasis, and cardiovascular and neuronal function. For the future, novel pharmacological strategies are emerging via small molecule epigenetic modulators, biologicals such as ETB monoclonal antibodies and the potential of signaling pathway biased agonists and antagonists.We (APD, JJM) thank the British Heart Foundation (PS/02/001, PG/05/127/19872, FS/12/64/130001), Wellcome Trust Programme in Metabolic and Cardiovascular Disease 096822/Z/11/Z NIHR Cambridge Biomedical Research Centre and the Pulmonary Hypertension Association UK; Wellcome Biomedical Resources Grant 099156/Z/12/Z for support for IUPHAR/BPS Guide to PHARMACOLOGY (CS). We acknowledge National Heart, Lung, and Blood Institute Grants P01 HL95499 (D.E.K., K.A.H., D.M.P., J.S.P.), P01 HL69999 (D.M.P., J.S.P.), U01HL117684 (D.M.P.).This is the final version of the article. It first appeared from the American Society for Pharmacology and Experimental Therapeutics via https://doi.org/10.1124/pr.115.01183

Gene expression profiling of Naïve sheep genetically resistant and susceptible to gastrointestinal nematodes

BACKGROUND: Gastrointestinal nematodes constitute a major cause of morbidity and mortality in grazing ruminants. Individual animals or breeds, however, are known to differ in their resistance to infection. Gene expression profiling allows us to examine large numbers of transcripts simultaneously in order to identify those transcripts that contribute to an animal's susceptibility or resistance. RESULTS: With the goal of identifying genes with a differential pattern of expression between sheep genetically resistant and susceptible to gastrointestinal nematodes, a 20,000 spot ovine cDNA microarray was constructed. This array was used to interrogate the expression of 9,238 known genes in duodenum tissue of four resistant and four susceptible female lambs. Naïve animals were used in order to look at genes that were differentially expressed in the absence of infection with gastrointestinal nematodes. Forty one unique known genes were identified that were differentially expressed between the resistant and susceptible animals. Northern blotting of a selection of the genes confirmed differential expression. The differentially expressed genes had a variety of functions, although many genes relating to the stress response and response to stimulus were more highly expressed in the susceptible animals. CONCLUSION: We have constructed the first reported ovine microarray and used this array to examine gene expression in lambs genetically resistant and susceptible to gastrointestinal nematode infection. This study indicates that susceptible animals appear to be generating a hyper-sensitive immune response to non-nematode challenges. The gastrointestinal tract of susceptible animals is therefore under stress and compromised even in the absence of gastrointestinal nematodes. These factors may contribute to the genetic susceptibility of these animals