Various heterotrimeric Gi proteins are considered to be involved in cell migration and effector function of immune cells. The underlying mechanisms, how they control the activation of myeloid effector cells, are not well understood. To elucidate isoform-redundant and -specific roles for Gαi proteins in these processes, we analyzed mice genetically deficient in Gαi2 or Gαi3. First, we show an altered distribution of tissue macrophages and blood monocytes in the absence of Gαi2 but not Gαi3. Gαi2-deficient but not wild-type or Gαi3-deficient mice exhibited reduced recruitment of macrophages in experimental models of thioglycollate-induced peritonitis and LPS-triggered lung injury. In contrast, genetic ablation of Gαi2 had no effect on Gαi-dependent peritoneal cytokine production in vitro and the phagocytosis-promoting function of the Gαi-coupled C5a anaphylatoxin receptor by liver macrophages in vivo. Interestingly, actin rearrangement and CCL2- and C5a anaphylatoxin receptor-induced chemotaxis but not macrophage CCR2 and C5a anaphylatoxin receptor expression were reduced in the specific absence of Gαi2. Furthermore, knockdown of Gαi2 caused decreased cell migration and motility of RAW 264.7 cells, which was rescued by transfection of Gαi2 but not Gαi3. These results indicate that Gαi2, albeit redundant to Gαi3 in some macrophage activation processes, clearly exhibits a Gαi isoform-specific role in the regulation of macrophage migration.
Durability is the most pressing issue preventing the efficient commercialization of polymer electrolyte membrane fuel cell (PEMFC) stationary and transportation applications. A big barrier to overcoming the durability limitations is gaining a better understanding of failure modes for user profiles. In addition, durability test protocols for determining the lifetime of PEMFCs are important factors in the development of the technology. These methods are designed to gather enough data about the cell/stack to understand its efficiency and durability without causing it to fail. They also provide some indication of the cell/stack’s age in terms of changes in performance over time. Based on a study of the literature, the fundamental factors influencing PEMFC long-term durability and the durability test protocols for both PEMFC stationary and transportation applications were discussed and outlined in depth in this review. This brief analysis should provide engineers and researchers with a fast overview as well as a useful toolbox for investigating PEMFC durability issues.
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