Pathogenic mechanisms that account for the dramatic differences between the HIV-1 and HIV-2 epidemics remain unknown. Myeloid dendritic cells (DCs) are sentinels of the immune system, which sense invading pathogens and initiate immune responses. I hypothesize that failure of HIV-2 to overcome DC-intrinsic defense mechanisms results in diminished virus replication and reduced pathogenesis in vivo. Recent studies from our laboratory have identified capture of HIV-1 by CD169 (Siglec1), which results in preservation of virus infectivity in peripheral non-lysosomal compartments and transfer to CD4+ T cells, a mechanism of DC-mediated trans infection. HIV-1 interaction with CD169 was dependent on incorporation of a ganglioside, GM3, in the virus particle membrane. We hypothesized that reduced interaction of HIV-2 with CD169 is crucial for its attenuated pathogenic phenotype in vivo. Interestingly, HIV-2 virion assembly sites were divergent from HIV-1, which correlated with reduced incorporation of GM3 in HIV-2 virions, and a significant decrease in capture of HIV-2 compared to HIV-1 by mature DCs. Furthermore, reduced CD169-dependent HIV-2 capture by DCs attenuated access of HIV-2 to DC-mediated trans infection. In contrast to the trans infection pathway, HIV-2 could establish productive infection in DCs, though productive infection of DCs by HIV-2 resulted in innate immune activation, induction of IFN-α production and attenuated spread of virus in DC – CD4+ T cell co-cultures. As opposed to HIV-2, productive infection of DCs by HIV-1 was attenuated and failed to trigger type I IFN responses, thus allowing for efficient spread of HIV-1 in DC – CD4+ T cell co-cultures. These results suggest that immune sensing of HIV-2 in productively infected DCs limits viral spread. Finally, we investigated GM3-expressing nanoparticles (GM3-NPs) for delivery of therapeutics that trigger innate immune responses in CD169+ myeloid cells as a novel strategy to mimic myeloid cell-intrinsic virus control observed in HIV-2 infection. We tested the ability of GM3-coated nanoparticles that incorporated a TLR2 ligand, Pam3CSK4, to activate CD169+ cells. Interestingly, Pam3CSK4 containing GM3-NPs robustly activated CD169+ cells. These results suggest that induction of dendritic cell-intrinsic type I IFN responses might be a fruitful therapeutic strategy to restrict HIV-1 replication in vivo.

In this thesis, non-binary people’s experience of gendered embodiment as well as inhabiting and navigating society is analysed. This is primarily done by using the theoretical framework of institutional lines, specifically applied through a trans studies perspective. Other important influences have been theories about how regulatory norms impact queer and trans subjectivities. Furthermore, special notice has been made of how social categorisations such as sexuality, class, and (dis)ability impact the non-binary subject’s experience of gender and of inhabiting society. This study is based on interview material produced through in-depth interviews with eleven non-binary Swedish people, as well as autoethnographical narratives produced by the author. The study shows that several different institutional lines impact the non-binary subject’s navigation through social space, as well as their experience of gendered embodiment. It was also clear that it was difficult for non-binary people to be recognised as coherent subjects, because of them breaking the regulatory norms that dictate intelligibility. Non-binary people are therefore often seen as the abject. This could be exacerbated if one not only deviated from the straight line of gender, but also from other lines and thus did not follow the expected trans line. It was clear that one’s experiences as a non-binary person could not fully be reduced to one’s position in relation to any specific line, be it gender, sexuality, class, or body normativity, but was rather a result of all those lines.

Detta arbete har undersökt vilka strategier spelutvecklare kan använda sig av för att skapapositiv transrepresentation i digitala spel. Vi har identifierat en brist på transkaraktärer ispel och sett återkommande stereotyper bland transkaraktärer i spel och media. Genomsemi-strukturerade intervjuer med tillhörande enkät har 8 transpersoner intervjuats för attsammanställa deras uppfattning om existerande representation samt om två unikatranskaraktärer vi skapat. Resultaten visade att deltagarna anser att det bör skapastranskaraktärer av varierande kroppsformer, bakgrunder, könsuttryck och stadier avtransition för att förstärka att alla transpersoner är olika och att undvika karikatyrer, fokuspå deras trauma och presenterande av alla transpersoner som androgyna. Generellt ansågsvåra karaktärer vara positiva transrepresentationer, däremot är de inte mallar för hur allatranskaraktärer bör designas. Mer forskning behövs för att vidga normalitetsbegreppet förvilka som accepteras i samhället då sättet representation visas påverkar människorsuppfattningar om minoritetsgrupper.

This article focuses on the dialogues within and between Disney's The Princess and The Frog and a 1930s animated series about a young Black boy-Little Ol' Bosko. Both films feature Black characters who navigate a fairy tale world set in the swamps of southern Jim Crow era America in which they grapple with fears about reductive and demeaning black film stereotypes. Although they are in some ways trapped within the white gaze of the film's meaning, I argue that in their fantasies, both Bosko and Tiana outmaneuver the regime of representation that underlies racial stereotyping, opening a space for trans-coding and revision of its meanings. In addition, a comparison of the films demonstrates a clear improvement from the 1930s in terms of an increased differentiation in the representation of Black Americans, acknowledging, if not embodying, the fact that "Black America" is a diverse and complex reality.

This essay explores how, for many minoritized peoples, cyborg ontology is experienced as dehumanizing rather than posthumanizing. Rereading Haraway’s Cyborg Manifesto through a decolonial, transfeminist lens, it explores the implications of Haraway’s assertion that cyborg subjectivity is the “illegitimate offspring of militarism and patriarchal capitalism” by examining the modern/colonial development and deployment of microprosthetic hormonal technologies–so often heralded as one of the technologies ushering in a queer, posthuman, post-gender future–as mechanisms of gendered and racialized subjective control operative at the level of the biomolecular.

Recent years have seen an unprecedented paradigm shift wherein pathologizing approaches to caring for trans children have been contested by efforts to accept and affirm trans children as their self-determined gender. This has resulted in a mainstreaming of gender affirming and de-pathologizing approaches to caring for trans children. While gender affirming care undoubtedly benefits many trans children, this research analyzes the ways in which practices and delivery of gender affirming care can be exclusionary of children who do not fit within a normative, binary, medicalized, white, and middle-class conceptualization of trans childhood. Applying critical social citizenship as a theoretical framework, this research argues that care for trans children is shaped through a complex interweaving of normative liberal citizenship regimes, professional and social care practices, and relational care practices that seek to recognize and create space for children to belong as their self-determined gender. Using a community-based research methodology to engage with trans youth and supportive parent caregivers around their experiences of care, this study sought to a) better understand how the contested landscape of care impacts the lives of trans children and b) offer possibilities for transforming care for trans children. Centring the voices and experiences of trans youth and parents, this research argues that trans children face exclusions and barriers when accessing care. This research then discusses what relational care practices, as shared in participant narratives, offer for envisioning care possibilities that centre trans children’s agency and gender self-determination. The outcome of this research is a vision of care for trans children that is rearticulated through a critical theorization of trans children’s citizenship. / Graduate

The essay aims to make a theoretical analysis of the consequenses from violence and its constitution of the subject. With the background of vulnerability for transgendered bodies in prostitition the analysis consist of the discussing reasons for the problematic capability to exit prostitution safely while still being able to dream of a social future life, and further the essay attempt to contribute with a discussion of how the mechanics of violence has fatal impacts for these vulnerable bodies. Conclusively, I will adress the importance of a more poststructural understanding of repercussions of violence to be able to offer an adequate social support. With the basis of a queer perspective of the ontology of death, primarily based on Judith Butler and Martin Heidegger, I will suggest a more radical erotogenizing of the body to constitute itself rather than on the basis hegemonic conventions.

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No description available.

Ribosomes stall on defective messenger RNA transcripts in eubacteria. Without a mechanism to release stalled ribosomes, these cells would die. Transfer-messenger RNA (tmRNA) and small protein B (SmpB) reactivate stalled ribosomes in a process known as trans-translation. Together, tmRNA and SmpB mimic alanyl-tRNA, entering the A site of stalled ribosomes and accepting transfer of the stalled polypeptide. A portion of tmRNA is then positioned as a template for the ribosome to resume translating. The tmRNA open reading frame encodes a proteolysis tag to mark the aberrant polypeptide for degradation and a stop codon to release the ribosome. How are tmRNA and SmpB allowed into stalled ribosomes? In normal translation, decoding mechanisms carefully monitor the anticodon of tRNAs entering the A site and select only those that are complementary to the mRNA codon. How do tmRNA and SmpB get around the decoding machinery? It appears that interactions between the SmpB C-terminal tail and the decoding center are responsible. Using an in vivo tagging assay and an in vitro peptidyl-transfer assay, we monitored the effect of mutations in the SmpB tail on trans-translation. We found that mutations in SmpB that prevent helix formation are unable to support peptidyl transfer. We also found that while mutation of key nucleotides in the ribosomal decoding center severely inhibit peptidyl transfer to normal tRNAs, these mutations do not inhibit peptidyl transfer to tmRNA. We conclude that the SmpB tail stimulates peptidyl transfer by forming a helix that interacts with the ribosome to signal decoding in a novel manner. How is the tmRNA open reading frame positioned for the ribosome to resume translating? Mutation of the tmRNA nucleotide A86 alters reading frame selection. Using a genetic selection, we identified SmpB mutants that restore normal frame selection to A86C tmRNA without altering frame selection on wild-type tmRNA. Through rational mutation of the SmpB tail we identified an SmpB mutant that supports peptidyl transfer but prevents translation of the tmRNA open reading frame. We conclude that SmpB plays a functional role in selecting the tmRNA open reading frame.