Queer In AI: A Case Study in Community-Led Participatory AI

Queerness and queer people face an uncertain future in the face of ever more widely deployed and invasive artificial intelligence (AI). These technologies have caused numerous harms to queer people, including privacy violations, censoring and downranking queer content, exposing queer people and spaces to harassment by making them hypervisible, deadnaming and outing queer people. More broadly, they have violated core tenets of queerness by classifying and controlling queer identities. In response to this, the queer community in AI has organized Queer in AI, a global, decentralized, volunteer-run grassroots organization that employs intersectional and community-led participatory design to build an inclusive and equitable AI future. In this paper, we present Queer in AI as a case study for community-led participatory design in AI. We examine how participatory design and intersectional tenets started and shaped this community’s programs over the years. We discuss different challenges that emerged in the process, look at ways this organization has fallen short of operationalizing participatory and intersectional principles, and then assess the organization’s impact. Queer in AI provides important lessons and insights for practitioners and theorists of participatory methods broadly through its rejection of hierarchy in favor of decentralization, success at building aid and programs by and for the queer community, and effort to change actors and institutions outside of the queer community. Finally, we theorize how communities like Queer in AI contribute to the participatory design in AI more broadly by fostering cultures of participation in AI, welcoming and empowering marginalized participants, critiquing poor or exploitative participatory practices, and bringing participation to institutions outside of individual research projects. Queer in AI’s work serves as a case study of grassroots activism and participatory methods within AI, demonstrating the potential of community-led participatory methods and intersectional praxis, while also providing challenges, case studies, and nuanced insights to researchers developing and using participatory methods

Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis.

All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA integrated as proviral sequences. This complicates efforts to define viral-induced mammary carcinogenesis. Here we report the use of surgical nonlethal splenectomy in tissue typing mice and the development of an MMTV-negative mouse strain. The MMTV-negative strain allows study of the involvement of non-MMTV genes in mammary carcinogenesis. In addition, it can be used as a sterile background into which MMTV variants can be introduced. Through the techniques described here, mice containing single MMTV loci or specific combinations can be specially chosen and rapidly developed. In this manner, the oncogenecity of particular MMTV variants may be assessed

Immunohistochemical Detection of Neural Stem Cells and Glioblastoma Stem Cells in the Subventricular Zone of Glioblastoma Patients

Glioblastoma usually recurs after therapy consisting of surgery, radiotherapy, and chemotherapy. Recurrence is at least partly caused by glioblastoma stem cells (GSCs) that are maintained in intratumoral hypoxic peri-arteriolar microenvironments, or niches, in a slowly dividing state that renders GSCs resistant to radiotherapy and chemotherapy. Because the subventricular zone (SVZ) is a major niche for neural stem cells (NSCs) in the brain, we investigated whether GSCs are present in the SVZ at distance from the glioblastoma tumor. We characterized the SVZ of brains of seven glioblastoma patients using fluorescence immunohistochemistry and image analysis. NSCs were identified by CD133 and SOX2 but not CD9 expression, whereas GSCs were positive for all three biomarkers. NSCs were present in all seven samples and GSCs in six out of seven samples. The SVZ in all samples were hypoxic and expressed the same relevant chemokines and their receptors as GSC niches in glioblastoma tumors: stromal-derived factor-1α (SDF-1α), C-X-C receptor type 4 (CXCR4), osteopontin, and CD44. In conclusion, in glioblastoma patients, GSCs are present at distance from the glioblastoma tumor in the SVZ. These findings suggest that GSCs in the SVZ niche are protected against radiotherapy and chemotherapy and protected against surgical resection due to their distant localization and thus may contribute to tumor recurrence after therapy

Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy?

Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and/or chemotherapy

Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches

Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches. Therefore, we determined expression of these cathepsins in serial paraffin sections of 14 human GBM samples and serial cryostat sections of two samples using immunohistochemistry and metabolic mapping of cathepsin activity using selective fluorogenic substrates. We detected cathepsins B, X and K in peri-arteriolar GSC niches in 9 out of 16 GBM samples, which were defined by co-expression of the GSC marker CD133, the niche marker stromal-derived factor-1α (SDF-1α) and smooth muscle actin as a marker for arterioles. The expression of cathepsin B and X was detected in stromal cells and cancer cells throughout the GBM sections, whereas cathepsin K expression was more restricted to arteriole-rich regions in the GBM sections. Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. On the basis of these findings, it is concluded that cathepsins B, X and K have distinct functions in GBM and that cathepsin K is the most likely GSC niche-related cathepsin of the three cathepsins investigated