Empathy rituals:Small conversations about emotional distress on Twitter

There is growing research interest in the sharing of emotions through social media. Usually centred on ‘newsworthy’ events and collective ‘flows’ of emotion, this work is often computationally driven. This article presents an interaction-led analysis of small data from Twitter to illustrate how this kind of intensive focus can ‘thicken’ claims about emotions, and particularly empathy. Drawing on Goffman’s work on ritual, we introduce and then apply the idea of ‘empathy rituals’ to exchanges about emotional distress on Twitter, a platform primarily researched using big data approaches. While the potential of Goffman’s work has been explored in some depth in relation to digital performances, its emotional dimension has been less fully examined. Through a focus on Twitter conversations, we show how reading small data can inform computational social science claims about emotions and add to sociological understanding of emotion in (digital) publics

Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2

Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, which interferes with orofacial function including talking and eating. We report that legumain (Lgmn) cleaves protease-activated receptor-2 (PAR2) in the acidic OSCC microenvironment to cause pain. Lgmn is a cysteine protease of late endosomes and lysosomes that can be secreted; it exhibits maximal activity in acidic environments. The role of Lgmn in PAR2-dependent cancer pain is unknown. We studied Lgmn activation in human oral cancers and oral cancer mouse models. Lgmn was activated in OSCC patient tumors, compared with matched normal oral tissue. After intraplantar, facial or lingual injection, Lgmn evoked nociception in wild-type (WT) female mice but not in female mice lacking PAR2 in NaV1.8-positive neurons (Par2Nav1.8), nor in female mice treated with a Lgmn inhibitor, LI-1. Inoculation of an OSCC cell line caused mechanical and thermal hyperalgesia that was reversed by LI-1. Par2Nav1.8 and Lgmn deletion attenuated mechanical allodynia in female mice with carcinogen-induced OSCC. Lgmn caused PAR2-dependent hyperexcitability of trigeminal neurons from WT female mice. Par2 deletion, LI-1, and inhibitors of adenylyl cyclase or protein kinase A (PKA) prevented the effects of Lgmn. Under acidified conditions, Lgmn cleaved within the extracellular N terminus of PAR2 at Asn30↓Arg31, proximal to the canonical trypsin activation site. Lgmn activated PAR2 by biased mechanisms in HEK293 cells to induce Ca2+ mobilization, cAMP formation, and PKA/protein kinase D (PKD) activation, but not β-arrestin recruitment or PAR2 endocytosis. Thus, in the acidified OSCC microenvironment, Lgmn activates PAR2 by biased mechanisms that evoke cancer pain.SIGNIFICANCE STATEMENT Oral squamous cell carcinoma (OSCC) is one of the most painful cancers. We report that legumain (Lgmn), which exhibits maximal activity in acidic environments, cleaves protease-activated receptor-2 (PAR2) on neurons to produce OSCC pain. Active Lgmn was elevated in OSCC patient tumors, compared with matched normal oral tissue. Lgmn evokes pain-like behavior through PAR2 Exposure of pain-sensing neurons to Lgmn decreased the current required to generate an action potential through PAR2 Inhibitors of adenylyl cyclase and protein kinase A (PKA) prevented the effects of Lgmn. Lgmn activated PAR2 to induce calcium mobilization, cAMP formation, and activation of protein kinase D (PKD) and PKA, but not β-arrestin recruitment or PAR2 endocytosis. Thus, Lgmn is a biased agonist of PAR2 that evokes cancer pain

Cathepsin S Evokes PAR(2)-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR2) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR2. We report here a role for cathepsin S in PAR2-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR2 in Nav1.8-positive neurons (Par2Nav1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR2 on neurons

The Divan Orchestra: Mutual Middle-range Transformation

An international couple builds bridges between enemies by involving them in a process of pacification and, at a deeper level, reconciliation. Following Norbert Elias's notion of double-bind, the influence of musicians and aesthetics on international conflict transformation is analysed. Namely, Edward Said and Daniel Barenboim embodied a middle-range couple in the Israeli-Palestinian conflict (between top leadership focusing on high-level negotiations and grassroots actors such as local leaders and non-governmental organizations), via new symbols of integration such as the West-Eastern Divan Workshop and Orchestra (young musicians from Israel and Arab countries), the Barenboim–Said foundation or a musical centre in Ramallah. As a couple, they developed initiatives to change perceptions of others by improving intercultural relations between Israelis, Arabs, and Palestinians, showing that music can play a significant role in conflict resolution. Still, they encountered inhibiting factors in the process of reconciliation, despite their shared views about linking music and politics