A framework for the joint institutionalization of climate change mitigation and adaptation in city administrations.

Cities are key actors in reducing both the causes of climate change (mitigation) and its impact (adaptation), and many have developed separate mitigation and adaptation strategies and measures. However, in order to maximize outcomes, both scholars and practitioners are increasingly calling for more integrated and synergetic approaches. Unfortunately, related research remains scarce and fragmented, and there is a lack of systematic investigation into the necessary institutional conditions and processes. Against this background, this paper develops a framework to assess and support the joint institutionalization of climate adaptation and mitigation-here called adaptigation-in city administrations. This pioneering framework draws upon four key features of bureaucracies: organizational structure, visions and goals, actors, and technology and tools. Illustrated by pilot applications to the cities of Würzburg (Germany) and Mwanza (Tanzania), the framework provides a robust basis for future research, policy recommendations, and the development of context-specific guidelines for national and local decision-makers and officials. It highlights the importance of (i) clearly defined procedures for the implementation of adaptigation into urban planning processes (e.g., with the active involvement of stakeholders in the form of working groups or roundtable discussions), (ii) locally relevant goals and visions, established in collaboration with stakeholders, and (iii) the creation of mitigation and adaptation structures that are supported by the appropriate level of human resources, both within and outside city administrations. In this context, global, supranational, and national institutions play an important role in supporting institutionalization by providing targeted funding and promoting adaptigation, which requires the development of integrated goals, visions, and legislation.

Induction of a hypertrophic growth status of coronary smooth muscle cells is associated with an overexpression of TGF-beta.

Hypertrophy of vascular smooth muscle cells occurs during hypertension-induced remodelling of arteries and during development of arteriosclerosis and restenosis following angioplasty but the pathogenesis of the hypertrophic status is not yet fully understood. In a previous study we demonstrated that the synthetic non-sulfated, non-toxic heparin-mimicking compound RG-13577 is capable of inducing a cell cycle-arrested hypertrophic phenotype of coronary smooth muscle cells. In this study we clarify the mode of action of RG-13577 and demonstrate that the RG-13577-induced hypertrophy is associated with an increased expression of TGF-beta1 as indicated by an increase in TGF-beta1-specific protein and mRNA level. Furthermore we show that RG-13577-treated hypertrophic smooth muscle cells maintain full metabolic activity as indicated by a continuous de novo synthesis of protein and proteoglycans and that the RG-13577-induced growth arrest is caused not only by a higher expression of TGF-beta, but also by a reduced response of RG-treated cells to the mitogenic activity of bFGF, PDGF and EGF. The growth inhibitory activity of RG-13577 is reduced in the presence of neutralizing antibodies against TGF-beta. TGF-beta itself has anti-proliferative activity in serum-depleted medium. The RG-13577 effect is reversible since incubation of hypertrophic cells in RG-13577-free medium restores cell volume and [3H]thymidine incorporation to the values of untreated control cells within 4 days. We conclude, that the active metabolic status of RG-13577-treated cells in association with the overexpression of TGF-beta could promote repair processes of injured arteries after angioplasty without stimulating cell proliferation.

High density lipoprotein-associated lysosphingolipids reduce E-selectin expression in human endothelial cells.

Adhesion and recruitment of blood monocytes, processes mediated by cell adhesion molecules including E-selectin, represent an early event in atherogenesis. High density lipoproteins (HDLs) were shown to inhibit cytokine-induced expression of adhesion molecules, but mechanisms underlying this effect are not fully understood. We here investigated the effects of sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), two lysosphingolipids associated with HDL, on TNF-alpha-induced E-selectin expression in human umbilical endothelial cells. We found that HDL, SPC, and LSF inhibited E-selectin expression both on mRNA and protein level. In addition, all three agents reduced the number of E-selectin molecules present on endothelial cell surface. The inhibitory effects of HDL, SPC, and LSF on TNF-alpha-induced E-selectin expression were partially reverted in the presence of suramin, an antagonist of lysosphingolipid receptor EDG-3, or pertussis toxin, an inhibitor of trimeric G proteins. In addition, inhibition of activation of protein kinase Akt with LY294002 but not inhibition of phosphatidylinositol-specific phospholipase C (PI-PLC) with U73122 abolished the restrictive effects of HDL-, SPC-, or LSF on E-selectin expression. We conclude that HDL-associated lysosphingolipids may at least partially account for the inhibitory effects of HDL on cytokine-induced expression of adhesion molecules, and that activations of G-protein-coupled receptors and protein kinase Akt are involved in this process.