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Evaluating social and economic development programs that involve community action and/or development is problematic due to their flexibility and complexity. The important elements of action research are established and incorporated into a method to evaluate the Empowerment Zone program.

The activation of the small GTPase ARF6 has been implicated in promoting several pathological processes related to vascular instability and tumor formation, growth, and metastasis. ARF6 also plays a vital role during embryonic development. Recent studies have suggested that ARF6 carries out these disparate functions primarily by controlling protein trafficking within the cell. ARF6 helps direct proteins to intracellular or extracellular locations where they function in normal cellular responses during development and in pathological processes later in life. This transport of proteins is accomplished through a variety of mechanisms, including endocytosis and recycling, microvesicle release, and as yet uncharacterized processes. This Commentary will explore the functions of ARF6, while focusing on the role of this small GTPase in development and postnatal physiology, regulating barrier function and diseases associated with its loss, and tumor formation, growth, and metastasis. [ABSTRACT FROM AUTHOR]

Familial melanoma is associated with point mutations in the cyclin-dependent kinase (CDK) inhibitor p16INK4A (p16). We recently reported that p16 regulates intracellular oxidative stress in a cell cycle-independent manner. Here we constructed 12 different familial melanoma-associated point mutants spanning the p16 coding region and analyzed their capacity to regulate cell cycle phase and suppress reactive oxygen species (ROS). Compared with wild-type p16, which fully restored both functions in p16-deficient fibroblasts, various p16 mutants differed in their capacity to normalize ROS and cell cycle profiles. Although some mutations did not impair either function, others impaired both. Interestingly, several mutations impaired cell cycle (R24Q, R99P, and V126D) or oxidative functions (A36P, A57V, and P114S) selectively, indicating that these two functions of p16 can be uncoupled. Similar activities were confirmed with selected mutants in human melanoma cells. Many mutations impairing both cell cycle and oxidative functions, or only cell cycle function, localize to the third ankyrin repeat of the p16 molecule. Alternatively, most mutations impairing oxidative but not cell cycle function, or those not impairing either function, lie outside this region. These results demonstrate that particular familial melanoma-associated mutations in p16 can selectively compromise these two independent tumor-suppressor functions, which may be mediated by distinct regions of the protein. [ABSTRACT FROM AUTHOR]

We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS) may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility. [ABSTRACT FROM AUTHOR]