Science
27 February 2015 vol 347, issue 6225, pages 921-1040
http://www.sciencemag.org/current.dtl

Review
Systems integration for global sustainability
Jianguo Liu1,*, Harold Mooney2, Vanessa Hull1, Steven J. Davis3, Joanne Gaskell4, Thomas Hertel5, Jane Lubchenco6, Karen C. Seto7, Peter Gleick8, Claire Kremen9, Shuxin Li1
Author Affiliations
1Center for Systems Integration and Sustainability, Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI, USA.
2Department of Biology, Stanford University, Stanford, CA, USA.
3Department of Earth System Science, University of California, Irvine, CA, USA.
4World Bank, Washington, DC, USA.
5Department of Agricultural Economics, Purdue University, West Lafayette, IN, USA.
6Department of Integrative Biology, Oregon State University, Corvallis, OR, USA.
7School of Forestry and Environmental Studies, Yale University, New Haven, CT, USA.
8The Pacific Institute, Oakland, CA, USA.
9Department of Environmental Science, Policy and Management, University of California, Berkeley, CA, USA.
Abstract
BACKGROUND
Many key global sustainability challenges are closely intertwined (examples are provided in the figure). These challenges include air pollution, biodiversity loss, climate change, energy and food security, disease spread, species invasion, and water shortages and pollution. They are interconnected across three dimensions (organizational levels, space, and time) but are often separately studied and managed. Systems integration—holistic approaches to integrating various components of coupled human and natural systems (for example, social-ecological systems and human-environment systems) across all dimensions—is necessary to address complex interconnections and identify effective solutions to sustainability challenges.

ADVANCES
One major advance has been recognizing Earth as a large, coupled human and natural system consisting of many smaller coupled systems linked through flows of information, matter, and energy and evolving through time as a set of interconnected complex adaptive systems. A number of influential integrated frameworks (such as ecosystem services, environmental footprints, human-nature nexus, planetary boundaries, and telecoupling) and tools for systems integration have been developed and tested through interdisciplinary and transdisciplinary inquiries. Systems integration has led to fundamental discoveries and sustainability actions that are not possible by using conventional disciplinary, reductionist, and compartmentalized approaches. These include findings on emergent properties and complexity; interconnections among multiple key issues (such as air, climate, energy, food, land, and water); assessment of multiple, often conflicting, objectives; and synergistic interactions in which, for example, economic efficiency can be enhanced while environmental impacts are mitigated. In addition, systems integration allows for clarification and reassignment of environmental responsibilities (for example, among producers, consumers, and traders); mediation of trade-offs and enhancement of synergies; reduction of conflicts; and design of harmonious conservation and development policies and practices.

OUTLOOK
Although some studies have recognized spillover effects (effects spilling over from interactions among other systems) or spatial externalities, there is a need to simultaneously consider socioeconomic and environmental effects rather than considering them separately. Furthermore, identifying causes, agents, and flows behind the spillover effects can help us to understand better and hence manage the effects across multiple systems and scales. Integrating spillover systems with sending and receiving systems through network analysis and other advanced analytical methods can uncover hidden interrelationships and lead to important insights. Human-nature feedbacks, including spatial feedbacks (such as those among sending, receiving, and spillover systems), are the core elements of coupled systems and thus are likely to play important roles in global sustainability. Systems integration for global sustainability is poised for more rapid development, and transformative changes aimed at connecting disciplinary silos are needed to sustain an increasingly telecoupled world.

Among Brazil, China, the Caribbean, and the Sahara Desert in Africa, there are complex human-nature interactions across space, time, and organizational levels. Deforestation in Brazil due to soybean production provides food for people and livestock in China. Food trade between Brazil and China also contributes to changes in the global food market, which affects other areas around the world, including the Caribbean and Africa, that also engage in trade with China and Brazil. Dust particles from the Sahara Desert in Africa—aggravated by agricultural practices—travel via the air to the Caribbean, where they contribute to the decline in coral reefs and soil fertility and increase asthma rates. These in turn affect China and Brazil, which have both invested heavily in Caribbean tourism, infrastructure, and transportation. Nutrient-rich dust from Africa also reaches Brazil, where it improves forest productivity.

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Perspective
Virology
Delineating Ebola entry
Darryl Falzarano1, Heinz Feldmann2
Author Affiliations
1Vaccine and Infectious Disease Organization–International Vaccine Centre, University of Saskatchewan, Saskatoon, SK Canada.
2Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT, USA.
The means by which Ebola virus enters a cell are becoming less mysterious. Although a definitive cell surface receptor for the virus, if there is one, remains to be identified, the mechanism of gaining entry is beginning to be fleshed out. Once inside the cell, the importance of numerous sequential processes is becoming better understood. On page 995 of this issue, Sakurai et al. (1) add another element to the viral entry pathway by showing that a calcium channel called two-pore channel 2 (TPC2) is required for release of the viral genome into the host cell.

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Report
Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment
Yasuteru Sakurai1, Andrey A. Kolokoltsov2, Cheng-Chang Chen3, Michael W. Tidwell4, William E. Bauta4, Norbert Klugbauer5, Christian Grimm3, Christian Wahl-Schott3, Martin Biel3, Robert A. Davey1,*
Author Affiliations
1Texas Biomedical Research Institute, San Antonio, TX, USA.
2The University of Texas Medical Branch, Galveston, TX, USA.
3Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy–Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.
4Southwest Research Institute, San Antonio, TX, USA.
5Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Abstract
Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy.