Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types (...) of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. (shrink)

Medical assistance in dying legislation in Canada followed much deliberation after the Supreme Court of Canada’s ruling in Carter v. Canada. Included in this deliberation was the Special Joint Committee on Physician Assisted Dying’s recommendation to extend MAID legislation beyond the inclusion of adults to mature minors. Children's agency is a construct advanced within childhood studies literature which entails eliciting children’s voices in order to recognise children as active participants in constructing their own childhoods. Using this framework, we consider the (...) possible extension of MAID legislation to most minors. We highlight important questions regarding how insights from children’s voices could be mobilised in the life or death context of MAID. We conclude that children’s voices have the potential to help determine their eligibility for MAID; however, incorporating children's voices in the context of MAID requires careful consideration due to the complexity of voice. (shrink)

The present paper analyses the Siddh Gosti, a composition of Guru Nanak to understand the interface of Guru Nanak’s philosophy with prevailing philosophical traditions of his time. The study views the composition as an effort on the part of the Guru to engage with and demolish the philosophical hegemony of an established belief system that held sway in Northwest India in order to make way for the establishment of his own philosophy. Guru Nanak does this by providing new interpretations of (...) constructs which the Siddhs and Naths concerned themselves with. These new interpretations were more practicable, socially relevant and humane as compared to the ways of the Siddh and Nath Yogi traditions thus making Sikhism a more acceptable religion. (shrink)

Classical treatise on the fundamentals of Nyaya philosophy with commentaries; critical edition.