The Suffering Joker and the Cruel Joke: Nabokov\u27s and Bellow\u27s Dark Laughter

This article interrogates the interrelationship between cruelty, suffering, and laughter in novels by Saul Bellow and Vladimir Nabokov, positing an affective reading of how bodies that suffer come to produce laughter as a confounding, unexpected, and at times inappropriate readerly affect. Nabokov’s Laughter in the Dark and Bellow’s Henderson the Rain King both explore suffering as a form of excessive somatic cruelty inflicted on protagonists who, in experiencing such punishment, engender a strange, troubling, and potentially transformative form of laughter. In order to bring together a discussion of the body, suffering, cruelty, and laughter in Nabokov and Bellow, the essay uses Henri Bergson\u27s idea of the elasticity of laughter in connection to cruelty and suffering, and various “affective” formulations of the body. In both writers, such Bergsonian elasticity of laughter is what allows for laughing at suffering, but there are crucial differences in their depictions of somatic suffering, particularly the responses they elicit from the reader. In Bellow\u27s Henderson the Rain King, it is the protagonist himself who jokes about his suffering body. In Nabokov\u27s Laughter in the Dark, it is the ironic narrator who simultaneously invites the reader to “laugh in the dark” and to check such laughter. What emerges in both novels is laughter as an unsettling readerly affect. Laughing about suffering thus may well become suffering after laughing, as the reader is forced to explore the emotional and ethical implications of such cruel laughter

Comparative Literature in Ireland and Worldwide – An Interview with Professor Declan Kiberd

Professor Declan Kiberd is Chair of Anglo-Irish Literature and Drama at University College Dublin, where he has taught for many years after having taught at the University of Kent at Canterbury and Trinity College Dublin. He is a director of the Abbey Theatre. He has been Parnell Fellow at Magdalene College Cambridge, and a visiting professor at Duke University and the Sorbonne. He has also been Director of the Yeats International Summer School (1985-7), Patron of the Dublin Shaw Society (1995-2000), a columnist with The Irish Times (1985-7) and The Irish Press (1987-93), the presenter of the RTÉ Arts programme, Exhibit A(1984-6), and a regular essayist and reviewer in The Irish Times, TLS,London Review of Books and The New York Times. Professor Kiberd is the author of many books including his seminal Inventing Ireland: The Literature of the Modern Nation (1995), Irish Classics (2000), and The Irish Writer and the World (2005), as well as Ulysses and Us, published just this year, and he was also the editor of the Penguin edition of theAnnotated Students’ Ulysses (1992). He is one of the most important voices in Irish Studies. Beyond that, he is also a prominent public intellectual, and he continues to be an inspirational figure for generations of students. In this interview, we discussed the relevance of the comparative approach to Irish Studies and the future of Comparative Literature in Ireland and worldwide

Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway

Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC.We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC-Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC-Treg clusters, indicating a role for adenosine in guiding DC-Treg interactions. Analysis of the signal transduction events in DC after contact to Treg revealed increased levels of cAMP, followed by activation of Epac1 and the GTPase Rap1. Subsequently activated Rap1 localized to the subcortical actin cytoskeleton in DC, providing a means by which directed locomotion of DC toward Treg is facilitated. In aggregate, these data show that Treg degrade ATP to adenosine via CD39, attracting DC by activating Epac1-Rap1-dependent pathways. As a consequence, DC-Treg clusters are formed and DC are rendered less stimulatory. This adenosine-mediated attraction of DC may therefore act as one mechanism by which Treg regulate the induction of immune responses by DC.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Immune-mediated necrotising myopathy: a critical review of current concepts

Immune-mediated necrotising myopathy (IMNM) is a relatively recently described form of idiopathic inflammatory myopathy (IIM) that is characterised by progressive proximal weakness and few extra-muscular manifestations. Prominent myonecrosis, muscle fibre regeneration and a relative paucity of intramuscular lymphocytes are seen histologically. Immunological mechanisms are believed to underpin the pathogenesis, and intense immunotherapy is frequently required. Disease is often severe and neuromuscular recovery may be poor. Recently there has been an impressive international research effort to understand and characterise this emerging condition, although much remains unknown. Significant advances in the field include the discovery of specific autoantibodies, increased understanding of the risk factors, clinical characteristics and treatment options owing to a wealth of observational studies, and the development of novel classification criteria. Herein we review the current evidence regarding the pathophysiology, clinical presentation, histological features and serological profiles associated with this condition. Diagnostic approaches are discussed, including the role of muscle MRI and antibodies targeting 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and signal-recognition peptide (SRP), and a review of current treatment recommendations is provided.Jessica A. Day, Vidya Limay

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Immune checkpoint inhibitors (ICIs) are increasingly used and are becoming the standard of care in the treatment of various tumour types. Despite the favourable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Neurological irAEs are rare but potentially severe. Neuromuscular disorders represent the most common neurological irAEs following anti-PD-1, anti-PDL-1 and anti-CTLA-4 treatment, and include myositis, myasthenia gravis and demyelinating polyradiculoneuropathy. Instrumental findings may differ from typical neuromuscular disorders occurring outside ICIs treatment. Despite initial severity, neurological irAEs often respond to immune-modulating therapies. Prompt irAEs diagnosis, ICIs discontinuation, and early treatment with corticosteroids, together with patient education and a multidisciplinary approach, are important for optimizing clinical outcomes. Intravenous immunoglobulin, plasma exchange and other immune-modulating treatments should be considered in more severe cases. Consideration of rechallenging with the same immunotherapy drug may be given in some cases, based on clinical picture and initial severity of irAEs. This article is protected by copyright. All rights reserved