Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation

Contains fulltext : 152899.pdf (Publisher’s version ) (Closed access)CARD9 is a central component of anti-fungal innate immune signaling via C-type lectin receptors, and several immune-related disorders are associated with CARD9 alterations. Here, we used a rare CARD9 variant that confers protection against inflammatory bowel disease as an entry point to investigating CARD9 regulation. We showed that the protective variant of CARD9, which is C-terminally truncated, acted in a dominant-negative manner for CARD9-mediated cytokine production, indicating an important role for the C terminus in CARD9 signaling. We identified TRIM62 as a CARD9 binding partner and showed that TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. We identified K125 as the ubiquitinated residue on CARD9 and demonstrated that this ubiquitination was essential for CARD9 activity. Furthermore, we showed that similar to Card9-deficient mice, Trim62-deficient mice had increased susceptibility to fungal infection. In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation

Sexual subjectification and <i>Bitchy Jones's Diary</i>

This paper presents the reflections of two academics on the blog Bitchy Jones's Diary (2006-2010), particularly its considerations of dominant femininity within the UK kink communities. Weaving together excerpts from the blog with our own dialogues, we consider the potentials of such a voice from within the communities in relation to more academic explorations. Specifically we focus on the relationship between Bitchy Jones's arguments and our own understandings of limited sexualised femininities available within wider culture, the place of agency within these, and the potentials for mutual recognition within both kinky, and non-kinky, relationships