Heterotopic Proliferation in E. S. Thomson’s Jem Flockhart Series

This article explores the convergence, inversion, and collapse of heterotopic spaces in E. S. Thomson’s neo-Victorian Jem Flockhart series about a cross-dressing female apothecary in mid-nineteenth-century London. The eponymous first-person narrator becomes embroiled in the detection of horrific murder cases, with the action traversing a wide range of Michel Foucault’s exemplary Other spaces, including hospitals, graveyards, brothels, prisons, asylums, and colonies, with the series substituting the garden for Foucault’s ship as the paradigmatic heterotopia. These myriad juxtaposed sites, which facilitate divergence from societal norms while seemingly sequestering forms of alterity and resistance, repeatedly merge into one another in Thomson’s novels, destabilising distinct kinds of heterotopias and heterotopic functions. Jem’s doubled queerness as a cross-dressing lesbian beloved by their Watsonean side-kick, the junior architect William Quartermain, complicates the protagonist’s role in helping readers negotiate the re-imagined Victorian metropolis and its unequal power structures. Simultaneously defending/reaffirming and contesting/subverting the status quo, Jem’s body itself becomes a microcosmic heterotopia, problematising the elision of agency in Foucault’s conceptualisation of the term. The proliferation of heterotopias in Thomson’s series suggests that neo-Victorian fiction reconfigures the nineteenth century into a vast network of confining, contested, and liberating Other spaces.

Tyrannous Minds and Tamed Bodies: The Curious Case of Irene Adler from Canon to Screen

Appearing in the singular short story “A Scandal in Bohemia” in Sir Arthur Conan Doyle’s Sherlock Holmes series, the character of Irene Adler has been adapted and reconstructed in subsequent literary and visual media. Twenty-first century screen adaptations have swivelled upon postfeminist re-appropriations of the character and overt sexualisation of the ‘body’, thereby engaging in reassessment of the Irene-Sherlock relationship and problematizing gendered presentations of the character. Locating Irene in a heteronormative space, such narratives have attempted to revise the image of the cross-dressing ‘adventuress’ through varied portrayals which seemingly broaden her scope by means of her deliberate transgressions of fixed gender tropes. This article, by taking into account the gendered power-play embedded in three popular twenty first century screen adaptations of the text, namely, the films Sherlock Holmes (2009) and Sherlock Holmes: A Game of Shadows (2011), CBS’s Elementary (2012-2019) and BBC’s Sherlock (2010-2017), scrutinizes the dilemma of presentation of Irene Adler through the lenses of sexual dynamics and gendered performances.

Nan King’s Orientation in Sarah Waters’s Tipping the Velvet: A Journey of Gender and Sexual Self-Discovery Following “The Slantwise Direction of Queer Desire”

In Tipping the Velvet (1998), Sarah Waters explores the notion of “gender performativity” as studied by Judith Butler (1990, 1993). Its protagonist, Nancy Astley, becomes aware of her sexuality and comes up with doubts about her gender as responding to the stable label society has put on her. This naïve girl moves from performing gender on stage to cross-dressing off-stage amid the crowds of London, not following, as Sarah Ahmed (2006) puts it, “the straight line” (p. 70). The aim of this paper is to explain how this straightness – both in terms of direction and heterosexuality – is the term Nancy, later on renamed Nan King, does not feel comfortable with. Throughout the novel, Nan’s discovery of a whole world of sexual and identity possibilities leads her to look for her own orientation, as her position in relation to the rest of “objects” around her is a queer one.

The Diva's Gift to the Shakespearean Stage

The Diva’s Gift to the Shakespearean Stage traces the transnational connections between Shakespeare’s all-male stage and the first female stars in the West. The book is the first to use Italian and English plays and other sources to explore this relationship, focusing on the gifted actress who radically altered female roles and expanded the horizons of drama just as the English were building their first paying theaters. By the time Shakespeare began to write plays, women had been acting professionally in Italian troupes for two decades, traveling across the Continent and acting in all genres, including tragicomedy and tragedy. Isabella Andreini, Vittoria Piissimi, and Barbara Flaminia became the first truly international stars, winning royal and noble patrons and literary admirers beyond Italy; their artistry enabled mixed companies to expand in foreign markets, especially in France and Spain. Elizabeth and her court caught wind of the Italians’ success, and soon troupes with actresses came to London to perform. Through contacts direct and indirect, English playwrights grew keenly aware of the mimetic revolution wrought by the skilled diva, who expanded the innamorata and made the type more engaging, outspoken, and autonomous. Some Englishmen pushed back, treating the actress as a whorish threat to the all-male stage, which had long minimized female roles. Others saw a vital new resource. Faced with rising demand for Italian-style plays, Lyly, Marlowe, Kyd, and Shakespeare used Italian models from scripted and improvised drama to turn out stellar female parts in the mode of the actress, altering them in significant ways while continuing to use boys to play them. Writers seized on the comici’s materials and methods to piece together pastoral, comic, and tragicomic plays from mobile theatergrams—plot elements, star scenes, roles, stories, and speeches, such as cross-dressing, mad scenes, and spoken and sung laments. Shakespeare and his peers gave new prominence to female characters, marked their passions as un-English, and devised plots that figured them as self-aware agents, not counters traded between men. Playing up the skills and charisma of the boy player, they produced stunning roles charged with the diva’s prodigious theatricality and alien glamour. Rightly perceived, the diva’s star persona and acclaimed performances constituted challenging and timely gifts that provoked English playwrights to break with the past in enormously generative ways.

The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?

Transplantation (Tx) remains the optimal therapy for end-stage disease (ESD) of various solid organs. Although alloimmune events remain the leading cause of long-term allograft loss, many patients develop innate and adaptive immune responses leading to graft tolerance. The focus of this review is to provide an overview of selected aspects of the effects of inflammation on this delicate balance following solid organ transplantation. Initially, we discuss the inflammatory mediators detectable in an ESD patient. Then, the specific inflammatory mediators found post-Tx are elucidated. We examine the reciprocal relationship between donor-derived passenger leukocytes (PLs) and those of the recipient, with additional emphasis on extracellular vesicles, specifically exosomes, and we examine their role in determining the balance between tolerance and rejection. The concept of recipient antigen-presenting cell “cross-dressing” by donor exosomes is detailed. Immunological consequences of the changes undergone by cell surface antigens, including HLA molecules in donor and host immune cells activated by proinflammatory cytokines, are examined. Inflammation-mediated donor endothelial cell (EC) activation is discussed along with the effect of donor-recipient EC chimerism. Finally, as an example of a specific inflammatory mediator, a detailed analysis is provided on the dynamic role of Interleukin-6 (IL-6) and its receptor post-Tx, especially given the potential for therapeutic interdiction of this axis with monoclonal antibodies. We aim to provide a holistic as well as a reductionist perspective of the inflammation-impacted immune events that precede and follow Tx. The objective is to differentiate tolerogenic inflammation from that enhancing rejection, for potential therapeutic modifications. (Words 247).

The Oxford Handbook of Queer Cinema

Queer media is not one thing but an ensemble of at least four moving variables: history, gender and sexuality, geography, and medium. Although many scholars would pinpoint the early 1990s as marking the emergence of a cinematic movement in the United States (dubbed by B. Ruby Rich the “new queer cinema”), films and television programs that clearly spoke to LGBTQ themes and viewers existed at many different historical moments and in many different forms: cross-dressing, same-sex attraction, comedic drag performance; at some points, for example, in 1950s television, these were not undercurrents but very prominent aspects of mainstream cultural production. Addressing “history” not as dots on a progressive spectrum but as an uneven story of struggle, the writers in this volume stress that queer cinema did not appear miraculously at one moment but arrived on currents throughout the century-long history of the medium. Likewise, while queer is an Anglophone term that has been widely circulated, it by no means names a unified or complete spectrum of sexuality and gender identity, just as the LGBTQ+ alphabet soup struggles to contain the distinctive histories, politics, and cultural productions of trans artists and genderqueer practices. Across the globe, media-makers have interrogated identity and desire through the medium of cinema through rubrics that sometimes vigorously oppose the Western embrace of the pejorative term queer, foregrounding instead indigenous genders and sexualities or those forged in the Global South or those seeking alternative epistemologies. Finally, though “cinema” is in our title, many scholars in this collection see this term as an encompassing one, referencing cinema and media in a convergent digital environment. The lively and dynamic conversations introduced here aspire to sustain further reflection as “queer cinema” shifts into new configurations.

683 Type-I-interferon activates cross-dressed CD11b+conventional dendritic cells to enhance anti-tumor immunity

BackgroundConventional dendritic cells (cDC) are critical mediators of protective anti-tumor CD8+ T-cell responses.1 Batf3-driven DC1 are the predominant cDC subset driving anti-tumor immunity due to their specialized ability to cross-present antigens for T-cell activation.2–4 However, the contribution of other tumor-infiltrating DC subsets such as CD11b+ DC2 to anti-tumor immunity remains poorly characterized. Recent studies suggest that under inflammation, DC subsets can exist in various functional states with differential impacts on their stimulatory potential.5–7 In this study, we sought to dissect the contributions of distinct DC states during a productive or dysfunctional anti-tumor immune response. A nuanced understanding of DC activation states in tumors and the signals that drive them carries therapeutic potential to modulate anti-tumor immunity and enhance immunotherapy responses.MethodsWe compared the DC infiltrate of a regressing tumor and a progressing tumor to study DC states. Flow immunophenotyping and RNA-sequencing was performed to profile the intratumoral DC compartment. Sorted DC subsets were co-cultured with T-cells ex vivo to evaluate their stimulatory capacity. Cross-dressing (in vivo/ex vivo) was assayed by staining for transfer of tumor-derived H-2b MHC complexes to MHC-mismatched or β2M-deficient DC.ResultsAnti-tumor CD8+ T-cell responses in Batf3-/- mice lacking DC1 were maintained in regressor tumors but not progressor tumors, suggesting DC1-independent anti-tumor immunity. Functional assays and RNA-sequencing of the intratumoral DC compartment of regressor tumors revealed a Zbtb46-dependent CD11b+ cDC activation state expressing an interferon-stimulated gene signature (ISG+ DC) that was critical for driving optimal anti-tumor CD8+ T-cell responses. Sorted ISG+ DC could activate CD8+ T-cells similar to DC1. Unlike cross-presenting DC1, however, ISG+ DC acquired antigens by cross-dressing with tumor-derived peptide-MHC, thereby bypassing the requirement for cross-presentation to initiate CD8+ T-cell-immunity. Interestingly, ISG+ DC were enriched in regressor tumors compared to progressor tumors, and this was attributable to constitutive tumor cell-intrinsic type-I-interferon (IFN-I) production in regressor tumors. Ablation of tumor cell-derived IFN-I in regressor tumors led to complete loss of anti-tumor T-cell responses in Batf3-/- mice. Conversely, addition of IFNβ to progressor tumors induced ISG+ DC and rescued anti-tumor T-cell responses in Batf3-/- mice.ConclusionsWe identified a novel IFN-I-induced activation state of CD11b+ cDC, called ISG+ DC, that was capable of driving anti-tumor CD8+ T cell immunity by cross-dressing with tumor-derived pMHC complexes in the absence of DC1. Engaging additional functional states of DC, such as ISG+ DC, will strengthen anti-tumor immunity and may improve immunotherapy responses.ReferencesMerad M, et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013;31:563–604Hildner K, et al. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 2008;322(5904)1097–100.Broz ML, et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 2014;26(5):638–52.Roberts EW, et al. Critical role for CD103(+)/CD141(+) dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in Melanoma. Cancer Cell 2016;30(2):324–336.Maier B, et al. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 2020;580(7802):257–262.Bosteels C, et al. Inflammatory Type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 2020;52(6):1039–1056.e9.Zilionis R, et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 2019;50(5):1317–1334.e10.