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Objective: Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion from pancreatic 13-cells. <br /> Methods: A 13-cell-specific Arfrp1 knockout mouse was phenotypically characterized. Pulldown experiments and mass spectrometry analysis were employed to screen for new ARFRP1-interacting proteins. Co-immunoprecipitation assays as well as super-resolution microscopy were applied for validation. <br /> Results: The GTPase ARFRP1 interacts with the Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). Both proteins are co localized at the trans-Golgi network and regulate the first and second phase of insulin secretion by controlling the plasma membrane localization of the SNARE protein SNAP25. Downregulation of both GOPC and ARFRP1 in Min6 cells interferes with the plasma membrane localization of SNAP25 and enhances its degradation, thereby impairing glucose-stimulated insulin release from 13-cells. In turn, overexpression of SNAP25 as well as GOPC restores insulin secretion in islets from 13-cell-specific Arfrp1 knockout mice. <br /> Conclusion: Our results identify a hitherto unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting. (c) 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Global emissions scenarios play a critical role in the assessment of strategies to mitigate climate change. The current scenarios, however, are criticized because they feature strategies with pronounced overshoot of the global temperature goal, requiring a long-term repair phase to draw temperatures down again through net-negative emissions. Some impacts might not be reversible. Hence, we explore a new set of net-zero CO2 emissions scenarios with limited overshoot. We show that upfront investments are needed in the near term for limiting temperature overshoot but that these would bring long-term economic gains. Our study further identifies alternative configurations of net-zero CO2 emissions systems and the roles of different sectors and regions for balancing sources and sinks. Even without net-negative emissions, CO2 removal is important for accelerating near-term reductions and for providing an anthropogenic sink that can offset the residual emissions in sectors that are hard to abate.
Land-based climate mitigation measures have gained significant attention and importance in public and private sector climate policies. Building on previous studies, we refine and update the mitigation potentials for 20 land-based measures in >200 countries and five regions, comparing “bottom-up” sectoral estimates with integrated assessment models (IAMs). We also assess implementation feasibility at the country level. Cost-effective (available up to $100/tCO2eq) land-based mitigation is 8–13.8 GtCO2eq yr−1 between 2020 and 2050, with the bottom end of this range representing the IAM median and the upper end representing the sectoral estimate. The cost-effective sectoral estimate is about 40% of available technical potential and is in line with achieving a 1.5°C pathway in 2050. Compared to technical potentials, cost-effective estimates represent a more realistic and actionable target for policy. The cost-effective potential is approximately 50% from forests and other ecosystems, 35% from agriculture, and 15% from demand-side measures. The potential varies sixfold across the five regions assessed (0.75–4.8 GtCO2eq yr−1) and the top 15 countries account for about 60% of the global potential. Protection of forests and other ecosystems and demand-side measures present particularly high mitigation efficiency, high provision of co-benefits, and relatively lower costs. The feasibility assessment suggests that governance, economic investment, and socio-cultural conditions influence the likelihood that land-based mitigation potentials are realized. A substantial portion of potential (80%) is in developing countries and LDCs, where feasibility barriers are of greatest concern. Assisting countries to overcome barriers may result in significant quantities of near-term, low-cost mitigation while locally achieving important climate adaptation and development benefits. Opportunities among countries vary widely depending on types of land-based measures available, their potential co-benefits and risks, and their feasibility. Enhanced investments and country-specific plans that accommodate this complexity are urgently needed to realize the large global potential from improved land stewardship.