31 research outputs found
dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic
Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome
Application of the Intervention Mapping protocol to develop Keys, a family child care home intervention to prevent early childhood obesity
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Subjectivity in a context of environmental change: opening new dialogues in mental health research
In a period of unstable experimentation with challenges of globalization of associated risks, and disenchantment with ‘enduring injustice’, we bring forward a consideration of subjectivity to the study of environmental change and mental health. We begin by identifying how mainstream climate change and mental health studies are unable to explain the emergent and co-evolutionary pathways of agency. As a means of freeing these studies of their objective dimensions of linear-causation, we argue in favour of a re-positioning of subjectivity within an appreciation of recognition conflicts and beyond the over-deterministic interpretations of power centres—state, market or religion. We draw on one example of scientific research that was conducted in a region undergoing strong environmental, social and cultural changes, in the state of São Paulo/Brazil, with the aim to open mental health research to new dialogues, to which we contribute with the notion of the ‘pluriversal subject’
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells
26sinoneNatural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.noneHammer Q.; Dunst J.; Christ W.; Picarazzi F.; Wendorff M.; Momayyezi P.; Huhn O.; Netskar H.K.; Maleki K.T.; Garcia M.; Sekine T.; Sohlberg E.; Azzimato V.; Aouadi M.; Degenhardt F.; Franke A.; Spallotta F.; Mori M.; Michaelsson J.; Bjorkstrom N.K.; Ruckert T.; Romagnani C.; Horowitz A.; Klingstrom J.; Ljunggren H.-G.; Malmberg K.-J.Hammer, Q.; Dunst, J.; Christ, W.; Picarazzi, F.; Wendorff, M.; Momayyezi, P.; Huhn, O.; Netskar, H. K.; Maleki, K. T.; Garcia, M.; Sekine, T.; Sohlberg, E.; Azzimato, V.; Aouadi, M.; Degenhardt, F.; Franke, A.; Spallotta, F.; Mori, M.; Michaelsson, J.; Bjorkstrom, N. K.; Ruckert, T.; Romagnani, C.; Horowitz, A.; Klingstrom, J.; Ljunggren, H. -G.; Malmberg, K. -J