␣-Galactosylceramide (␣-GalCer) is the prototype compound for studying the presentation of glycolipids on CD1d molecules to natural killer T (NKT) lymphocytes. A single i.v. dose of glycolipid triggers a cascade of events involving the production of several cytokines over the course of a day, a short-lived activation of NKT and natural killer (NK) cells, and a more prolonged adaptive T cell immune response if certain antigens are given together with ␣-GalCer. We find that a recently described analogue, ␣-C-galactosylceramide (␣-C-GalCer), more potently induces these innate and adaptive immune responses in mice. ␣-C-GalCer acts as a more effective trigger for IL-12 and IFN-␥ production, although it minimally elicits IL-4 and TNF-␣ release into the serum. Also, ␣-C-GalCer better mobilizes NKT and natural killer cells to resist B16 melanoma. To help understand these effects, we find that ␣-C-GalCer binds more stably to dendritic cells than ␣-GalCer and that dendritic cells loaded with ␣-C-GalCer induce larger and more long lasting NKT cell responses in vivo. When glycolipid is targeted to dendritic cells in spleen together with antigens in dying cells, such as irradiated tumor cells, ␣-C-GalCer is active as an adjuvant for T cell-mediated immunity at lower doses, just 20 ng per mouse, where it is also able to up-regulate the required CD40L costimulatory molecule on NKT cells. Therefore, ␣-C-GalCer represents a glycolipid that binds more stably to dendritic cells and acts as a more effective link between innate and adaptive immunity in vivo.immune therapy ͉ maturation ͉ natural killer T ͉ CD40L

No abstract

Summary Cities are thought to be associated with most of humanity's consumption of natural resources and impacts on the environment. Cities not only constitute major centers of economic activity, knowledge, innovation, and governance—they are also said to be linked to approximately 70% to 80% of global carbon dioxide emissions. This makes cities primary agents of change in a resource‐ and carbon‐constraint world. In order to set meaningful targets, design successful policies, and implement effective mitigation strategies, it is important that greenhouse gas (GHG) emissions accounting for cities is accurate, comparable, comprehensive, and complete. Despite recent developments in the standardization of city GHG accounting, there is still a lack of consistent guidelines regarding out‐of‐boundary emissions, thus hampering efforts to identify mitigation priorities and responsibilities. We introduce a new conceptual framework—based on environmental input‐output analysis—that allows for a consistent and complete reconciliation of direct and indirect GHG emissions from a city. The “city carbon map” shows local, regional, national, and global origins and destinations of flows of embodied emissions. We test the carbon map concept by applying it to the greater metropolitan area of Melbourne, Australia. We discuss the results and limitations of the approach in the light of possible mitigation strategies and policies by different urban stakeholders.

No abstract