Die Regenbogenparade als Praxis sozialen Protesthandelns

Die Regenbogenparade findet seit 1996 jährlich auf der Wiener Ringstraße statt. Sie steht in der Tradition von internationalen Pride-Paraden, die sich in der Folge der sogenannten stonewall riots in New York im Jahr 1969 entwickelt haben, und wurde von den Initiatoren als Demonstration mit Partycharakter konzipiert. Die TeilnehmerInnen machen sich die Form der Parade zunutze und ziehen begleitet von Trucks mit Musik über den Wiener Ring. Auf der Parade sind verkleidete Personen ebenso vertreten wie Personen in Alltagskleidung oder thematisch bedruckten T-Shirts. Viele teilnehmende Gruppen tragen Transparente und andere Kommunikationsmittel, um auf die von ihnen vertretenen Forderungen aufmerksam zu machen. Diese Gruppen koexistieren auf der Regenbogenparade mit kommerziellen Unternehmen und politischen Parteien. Durch diese Koexistenz und aufgrund der verschiedenen Aspekte der Parade fällt es schwer, die Regenbogenparade eindeutig einer Kategorie zuzuordnen. Einerseits steht sie in der Tradition von Festen und Karnevalsumzügen, andererseits kann sie als Event bezeichnet werden und weist einen gewissen Performancecharakter auf. Nicht zuletzt ist die Regenbogenparade jedoch auch eine Praxis sozialen Protesthandelns, da es darum geht, öffentlich Einspruch gegen die Marginalisierung und Diskriminierung von Schwulen, Lesben, Bisexuellen und Transgenderpersonen zu erheben und eine Veränderung dieser Verhältnisse zu fordern. Um diese Ziele zu erreichen, bedient sich die Regenbogenparade in erster Linie der Protestform der Demonstration. Die Legitimität der Regenbogenparade als eine Protestform wird aufgrund ihrer festlichen, karnevalesken Elemente oft angezweifelt, was nicht zuletzt an der Darstellung der Regenbogenparade in den Medien liegt. Letztendlich liegt die Wirkungskraft der Regenbogenarpade jedoch im Auge des Betrachters bzw. der Betrachterin

Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer

Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors. The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.Peer reviewe

Telehealth effectiveness for pre-exposure prophylaxis delivery in Brazilian public services : the Combine! Study

Introduction Pre-exposure prophylaxis (PrEP) delivery based on user needs can enhance PrEP access and impact. We examined whether telehealth for daily oral PrEP delivery could change the indicators of care related to prophylactic use in five Brazilian public HIV clinics (testing centres, outpatient clinics and infectious disease hospitals). Methods Between July 2019 and December 2020, clients on PrEP for at least 6 months could transition to telehealth or stay with in-person follow-up. Clients were clinically monitored until June 2021. A desktop or mobile application was developed, comprising three asynchronous consultations and one annual in-person consultation visit. Predictors influencing telehealth preference and care outcomes were examined. The analysis encompassed intent-to-treat (first choice) and adjustments for sexual practices, schooling, age, duration of PrEP use and PrEP status during the choice period. Results Of 470 users, 52% chose telehealth, with the adjusted odds ratio (aOR) increasing over time for PrEP use (aOR for 25–months of use: 4.90; 95% CI: 1.32–18.25), having discontinued PrEP at the time of the choice (aOR: 2.91; 95% CI: 1.40–6.06) and having health insurance (aOR: 1.91; 95% CI: 1.24–2.94) and decreasing for those who reported higher-risk behaviour (aOR for unprotected anal sex: 0.51; 95% CI: 0.29–0.88). After an average follow-up period of 1.6 years (95% CI: 1.5–1.7), the risk of discontinuing PrEP (not having the medication for more than 90 days) was 34% lower with telehealth (adjusted hazard ratio: 0.66; 95% CI: 0.45–0.97). When adjusted by mixed linear regression, no differences in adherence (measured by mean medication possession rate) were found between in-person and telehealth (p = 0.486) or at pre- and post-telehealth follow-ups (p = 0.245). Sexually transmitted infections increased between the pre-follow-up and post-follow-up choices and were not associated with in-person or telehealth (p = 0.528). No HIV infections were observed. Conclusions Our findings indicate that telehealth for PrEP delivery can enhance service rationalization and reinforce the prevention cascade. This approach reduces prophylaxis interruptions and is mainly preferred by individuals with lower demands for healthcare services

Development of self-reactive germinal center B cells and plasma cells in autoimmune FcγRIIB-deficient mice

The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning

Global fine-resolution data on springtail abundance and community structure

Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.</p

Co-targeting MCL-1 and ERK1/2 kinase induces mitochondrial apoptosis in rhabdomyosarcoma cells

The RAS/MEK/ERK genetic axis is commonly altered in rhabdomyosarcoma (RMS), indicating high activity of downstream effector ERK1/2 kinase. Previously, we have demonstrated that inhibition of the RAS/MEK/ERK signaling pathway in RMS is insufficient to induce cell death due to residual pro-survival MCL-1 activity. Here, we show that the combination of ERK1/2 inhibitor Ulixertinib and MCL-1 inhibitor S63845 is highly synergistic and induces apoptotic cell death in RMS in vitro and in vivo. Importantly, Ulixertinib/S63845 co-treatment suppresses long-term survival of RMS cells, induces rapid caspase activation and caspase-dependent apoptosis. Mechanistically, Ulixertinib-mediated upregulation of BIM and BMF in combination with MCL-1 inhibition by S63845 shifts the balance of BCL-2 proteins towards a pro-apoptotic state resulting in apoptosis induction. A genetic silencing approach reveals that BIM, BMF, BAK and BAX are all required for Ulixertinib/S63845-induced apoptosis. Overexpression of BCL-2 rescues cell death triggered by Ulixertinib/S63845 co-treatment, confirming that combined inhibition of ERK1/2 and MCL-1 effectively induces cell death of RMS cells via the intrinsic mitochondrial apoptotic pathway. Thus, this study is the first to demonstrate the cytotoxic potency of co-inhibition of ERK1/2 and MCL-1 for RMS treatment

Concepts of extracellular matrix remodelling in tumour progression and metastasis.

Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients