Loss of CD103+ DCs and Mucosal IL-17+ and IL-22+ Lymphocytes is Associated with Mucosal Damage in SIV Infection

HIV/SIV disease progression is associated with multifocal damage to the GI tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of IL-17-producing lymphocytes, cells that microarray analysis showed express genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ DCs after SIV infection which associated with loss of IL-17 and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and co-culture of CD103+ DCs and naïve T-cells led to increased IL17A and RORc expression in differentiating T-cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis

The screen test 1915–1930:how stars were born

This article examines the emergence of the screen test as a cultural phenomenon during the silent era in the US and Europe and its role in the development of the star system. The lore that grew up around the screen test almost from its inception held out the possibility for members of the public to cross a threshold into the rarefied world of celebrity. The screen test itself is situated in the liminal space not only between audience and actor, but also between fiction and non-fiction, Europe and Hollywood, the silent era and the talkies, and the public and private spheres. In order to trace the ways in which the screen test as such was narrativized and conceptualized in its foundational stages, this article will analyse accounts from Hollywood and European fan magazines of the silent era, including articles, short fiction, and early cinema apocrypha. The article culminates in a discussion of the film Prix de Beauté / Beauty Prize (Augusto Genina, 1930), which starred Louise Brooks, herself a transnational film icon whose film career spanned the divide between Hollywood and Europe. The film’s final scene, in which a beauty queen is shot dead by her jealous husband as she watches a screen test of herself, has been invoked by a number of film scholars as an allegory of the work performed by cinema, which preserves and disseminates the image of the star far beyond the actor’s physical presence. Speaking to historical conditions of star-making while also capturing its resonance in cultural mythology, the conclusion of Prix de Beauté allows us to consider the origins and functions of screen test discourse itself

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Consumer Bankruptcy Update

Materials from the Consumer Bankruptcy Update presentations held by UK/CLE in December 2000

A glimpse into Thurston's work

We present an overview of some significant results of Thurston and their impact on mathematics. The final version of this paper will appear as Chapter 1 of the book "In the tradition of Thurston: Geometry and topology", edited by K. Ohshika and A. Papadopoulos (Springer, 2020)

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514