Challenges to adaptation: a fundamental concept for the shared socio-economic pathways and beyond

The framework for the new scenarios being developed for climate research calls for the development of a set of Shared Socioeconomic Pathways (SSPs), which are meant to differ in terms of their challenges to mitigation and challenges to adaptation. In order for the scenario process to fulfill its goals, the research and policy communities need to develop a shared understanding of these concepts. This paper focuses on challenges to adaptation. We begin by situating this new concept in the context of the rich literatures related to inter alia adaptation, vulnerability, and resilience. We argue that a proper characterization of challenges to adaptation requires a rich, exploration of the concept, which goes beyond mere description. This has a number of implications for the operationalization of the concept in the basic and extended versions of the SSPs. First, the elements comprising challenges to adaptation must include a wide range of socioeconomic and even some (non-climatic) biophysical factors. Second, careful consideration must be given to differences in these factors across scales, as well as cross-scale interactions. Third, any representation of the concept will require both quantitative and qualitative elements. The scenario framework offers the opportunity for the SSPs and full scenarios to be of greater value than has been the case in past exercises to both Integrated Assessment Modeling (IAM) and Impacts,Adaptation, and Vulnerability (IAV) researchers, but this will require a renegotiation of the traditional, primarily unidirectional relationship between the two communities

Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies