Optical functionalization of human Class A orphan G-protein-coupled receptors

G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.</p

Language and identity among British South Asians: a theoretical review.

Given the pervasiveness of language in social life and the implications that language use can have for one’s individual and collective identities, attempts were made to explore the theoretical and empirical advantages in connecting social psychological theories of identity and sociological/sociolinguistic approaches to language use and language choices in order to make sense of language and identity among second-generation British Asians. The current theoretical essay features a brief overview of the sociology of British Asians in the United Kingdom and a detailed consideration of dominant theories of identity in social psychology, namely, Social Identity Theory Tajfel (1982), Self-Aspects Model of Identity (Simon 2004) and Identity Process Theory (Breakwell 1986). It is considered that the latter two theories lend themselves readily to the study of language and identity. The present essay considers the substantive literature on language and identity and deconstructs notions such as ‘mother tongue’ in an attempt to demonstrate the constructedness of such terminology. It is argued that a social psychological approach to questions of language and identity among British South Asians is a valid one and that a qualitative methodological approach is particularly well-suited to the area under investigation