Trade in the balance: reconciling trade and climate policy: report of the Working Group on Trade, Investment, and Climate Policy

This repository item contains a report published by the Working Group on Trade, Investment, and Climate Policy at The Frederick S. Pardee Center for the Study of the Longer-Range Future at Boston University, and the Global Economic Governance Initiative at Boston University.This report outlines the general tensions between the trade and investment regime and climate policy, and outlines a framework toward making trade and investment rules more climate friendly. Members of the working group have contributed short pieces addressing a range of issues related to the intersection of trade and climate policy. The first two are by natural scientists. Anthony Janetos discusses the need to address the effects of international trade on efforts to limit the increase in global annual temperature to no more than 2oC over preindustrial levels. James J. Corbett examines the failure of the Trans Pacific Partnership (TPP) and the Transatlantic Trade and Investment Partnership (TTIP) to adequately address the environmental implications of shipping and maritime transport. The next two pieces are by economists who examine economic aspects of the trade-climate linkage. Irene Monasterolo and Marco Raberto discuss the potential impacts of including fossil fuel subsidies reduction under the TTIP. Frank Ackerman explores the economic costs of efforts to promote convergence of regulatory standards between the United States and the European Union under the TTIP. The following two contributions are by legal scholars. Brooke Güven and Lise Johnson explore the potential for international investment treaties to redirect investment flows to support climate change mitigation and adaptation, particularly with regard to China and India. Matt Porterfield provides an overview of the ways in which both existing and proposed trade and investment agreements could have either “climate positive” or “climate negative” effects on mitigation policies. The final article is by Tao Hu, a former WTO trade and environment expert advisor for China and currently at the World Wildlife Fund, arguing that the definition of environmental goods and services’ under the WTO negotiations needs to be expanded to better incorporate climate change

Trade in the balance: reconciling trade and climate policy: report of the Working Group on Trade, Investment, and Climate Policy

This repository item contains a report published by the Working Group on Trade, Investment, and Climate Policy at The Frederick S. Pardee Center for the Study of the Longer-Range Future at Boston University, and the Global Economic Governance Initiative at Boston University.This report outlines the general tensions between the trade and investment regime and climate policy, and outlines a framework toward making trade and investment rules more climate friendly. Members of the working group have contributed short pieces addressing a range of issues related to the intersection of trade and climate policy. The first two are by natural scientists. Anthony Janetos discusses the need to address the effects of international trade on efforts to limit the increase in global annual temperature to no more than 2oC over preindustrial levels. James J. Corbett examines the failure of the Trans Pacific Partnership (TPP) and the Transatlantic Trade and Investment Partnership (TTIP) to adequately address the environmental implications of shipping and maritime transport. The next two pieces are by economists who examine economic aspects of the trade-climate linkage. Irene Monasterolo and Marco Raberto discuss the potential impacts of including fossil fuel subsidies reduction under the TTIP. Frank Ackerman explores the economic costs of efforts to promote convergence of regulatory standards between the United States and the European Union under the TTIP. The following two contributions are by legal scholars. Brooke Güven and Lise Johnson explore the potential for international investment treaties to redirect investment flows to support climate change mitigation and adaptation, particularly with regard to China and India. Matt Porterfield provides an overview of the ways in which both existing and proposed trade and investment agreements could have either “climate positive” or “climate negative” effects on mitigation policies. The final article is by Tao Hu, a former WTO trade and environment expert advisor for China and currently at the World Wildlife Fund, arguing that the definition of environmental goods and services’ under the WTO negotiations needs to be expanded to better incorporate climate change

A microarray analysis of full depth knee cartilage of ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.</p> <p>Findings</p> <p>We investigated, which extracellular matrix (ECM) protein, proteases and different pro-inflammatory factors was up- or down-regulated in the knee joint tissue in response to estrogen-deficiency in rats induced by ovariectomy. These data support previous findings that several metalloproteinases (MMPs) and cysteine proteases are co-regulated with numerous collagens and proteoglycans that are important for cartilage integrity. Furthermore quite a few pro-inflammatory cytokines were regulated by estrogen deprivation.</p> <p>Conclusion</p> <p>We found multiple genes where regulated in the joint by estrogen-deficiency, many of which correspond well with our current knowledge of the pathogenesis of OA. It supports that estrogen-deficiency (e.g. OVX) may accelerate joint deterioration. However, there are also data that draw attention the need for better understanding of the synergy between proteases and tissue turnover.</p

Pharmacological characterization of a novel 5-hydroxybenzothiazolone-derived b2-adrenoceptor agonist with functional selectivity for anabolic effects on skeletal muscle resulting in a wider cardiovascular safety window in preclinical studies

Copyright ª 2019 by The Author(s) The anabolic effects of b2-adrenoceptor (b2-AR) agonists on skeletal muscle have been demonstrated in various species. However, the clinical use of b2-AR agonists for skeletal muscle wasting conditions has been limited by their undesired cardiovascular effects. Here, we describe the preclinical pharmacological profile of a novel 5-hydroxybenzothiazolone (5-HOB) derived b2-AR agonist in comparison with formoterol as a representative b2-AR agonist that have been well characterized. In vitro, 5-HOB has nanomolar affinity for the human b2-AR and selectivity over the b1-AR and b3-AR. 5-HOB also shows potent agonistic activity at the b2-AR in primary skeletal muscle myotubes and induces hypertrophy of skeletal muscle myotubes. Compared with formoterol, 5-HOB demonstrates comparable full-agonist activity on cAMP production in skeletal muscle cells and skeletal muscle tissue–derived membranes. In contrast, a greatly reduced intrinsic activity was determined in cardiomyocytes and cell membranes prepared from the rat heart. In addition, 5-HOB shows weak effects on chronotropy, inotropy, and vascular relaxation compared with formoterol. In vivo, 5-HOB significantly increases hind limb muscle weight in rats with attenuated effects on heart weight and ejection fraction, unlike formoterol. Furthermore, changes in cardiovascular parameters after bolus subcutaneous treatment in rats and rhesus monkeys are significantly lower with 5-HOB compared with formoterol. In conclusion, the pharmacological profile of 5-HOB indicates superior tissue selectivity compared with the conventional b2-AR agonist formoterol in preclinical studies and supports the notion that such tissue-selective agonists should be investigated for the safe treatment of muscle-wasting conditions without cardiovascular limiting effects

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population