The adaptor protein FADD and the initiator caspase-8 mediate activation of NF-κB by TRAIL.

Besides inducing apoptosis, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates NF-κB. The apoptosis signaling pathway of TRAIL is well characterized involving TRAIL receptors, Fas-associated protein with death domain (FADD) and caspase-8. In contrast, the molecular mechanism of TRAIL signaling to NF-κB remains controversial. Here, we characterized the receptor-proximal mediators of NF-κB activation by TRAIL. Deletion of the DD of TRAIL receptors 1 and 2 revealed that it is essential in NF-κB signaling. Because FADD interacts with the TRAIL receptor DD, FADD was tested. RNAi-mediated knockdown of FADD or FADD deficiency in JURKAT T-cell leukemia cells decreased or disabled NF-κB signaling by TRAIL. In contrast, TRAIL-induced activation of NF-κB was maintained upon loss of receptor interacting protein 1 (RIP1) or knockdown of FLICE-like inhibitory protein (FLIP). Exogenous expression of FADD rescued TRAIL-induced NF-κB signaling. Loss-of-function mutations of FADD within the RHDLL motif of the death effector domain, which is required for TRAIL-induced apoptosis, abrogated FADD's ability to recruit caspase-8 and mediate NF-κB activation. Accordingly, deficiency of caspase-8 inhibited TRAIL-induced activation of NF-κB, which was rescued by wild-type caspase-8, but not by a catalytically inactive caspase-8 mutant. These data establish the mechanism of TRAIL-induced NF-κB activation involving the TRAIL receptor DD, FADD and caspase-8, but not RIP1 or FLIP. Our results show that signaling of TRAIL-induced apoptosis and NF-κB bifurcates downstream of caspase-8

Staging choreographies for team training in multiple virtual worlds based on ontologies and alignments

In this paper we present an approach that makes possible the staging of choreographies for education and training purposes in potentially any virtual world platform. A choreography is seen here as the description of a set of actions that must or may be executed by a group of participants, including the goals to be achieved and any restrictions that may exist. We present a system architecture and the formalization of a set of processes that are able to transform a choreography from a platform-independent representation into a specific virtual world platform’s representation. We adopt an ontology-based approach with distinct levels of abstraction for capturing and representing multi-actors and multi-domain choreographies to be staged in virtual world platforms with distinct characteristics. Ontologies are characterized according to two complementary dimensions – choreography’s domain (independent and dependent) and virtual world platform (independent and dependent) – giving rise to four ontologies. Ontology mappings between these ontologies enable the automatic generation of a choreography for virtually any target virtual world platform, thus reducing the time and effort of the choreography development

Model-driven generation of multi-user and multi-domain choreographies for staging in multiple virtual world platforms

Conferência internacional, realizada no Chipre de 24-26 de setembro de 2014This paper presents an approach that enables the staging of choreographies for education and training purposes in multiple virtual world platforms. Choreography is the description of a set of actions that must or may be executed by a group of participants, including the goals to be achieved and any restrictions that may exist. For capturing and representing multi-actor multi-domain choreographies an approach based on ontologies with distinct levels of abstraction is adopted. Further, this paper proposes a modelling driven approach and a set of processes that, through mappings between ontologies, enable the automatic construction of a platform-specific choreography from a platform-independent one, thus reducing the time and effort of the choreography development. For this, the MDA paradigm was adopted and adapted in a way where models can reflect two dimensions of independence: platform independence and application domain independence. We also point the guidelines for staging the choreography in a virtual world platform