Keratinocyte-specific ablation of the NF-kappa B regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis

The ubiquitin-editing enzyme A20 (tumor necrosis factor-alpha-induced protein 3) serves as a critical brake on nuclear factor kappa B (NF-kappa B) signaling. In humans, polymorphisms in or near the A20 gene are associated with several inflammatory disorders, including psoriasis. We show here that epidermis-specific A20-knockout mice (A20(EKO)) develop keratinocyte hyperproliferation, but no signs of skin inflammation, such as immune cell infiltration. However, A20(EKO) mice clearly developed ectodermal organ abnormalities, including disheveled hair, longer nails and sebocyte hyperplasia. This phenotype resembles that of mice overexpressing ectodysplasin-A1 (EDA-A1) or the ectodysplasin receptor (EDAR), suggesting that A20 negatively controls EDAR signaling. We found that A20 inhibited EDAR-induced NF-kappa B signaling independent from its de-ubiquitinating activity. In addition, A20 expression was induced by EDA-A1 in embryonic skin explants, in which its expression was confined to the hair placodes, known to be the site of EDAR expression. In summary, our data indicate that EDAR-induced NF-kappa B levels are controlled by A20, which functions as a negative feedback regulator, to assure proper skin homeostasis and epidermal appendage development. Cell Death and Differentiation (2011) 18, 1845-1853; doi:10.1038/cdd.2011.55; published online 13 May 201

Enterprise architecture for small and medium-sized enterprises: a starting point for bringing EA to SMEs, based on adoption models

Enterprise architecture (EA) is used as a holistic approach to keep things aligned in a company. Some emphasize the use of EA to align IT with the business, others see it broader and use it to also keep the processes aligned with the strategy. EA has gained importance in larger companies. Although a lot of research is being done on EA, still hardly anything is known about its use in the context of a small and medium-sized enterprise (SME). Although EA can offer a lot of benefits to SMEs, still hardly any SME uses EA. In this paper, the authors analyze both SMEs and EA techniques and investigate the adoption of EA in SMEs. At the end of the chapter, some guidelines for EA technique developers are proposed