83 research outputs found
Imposter Participants in Online Qualitative Interviews: A Protocol for Trauma-Informed and Equitable Decision-Making
Imposter participants are an emerging concern in qualitative research due to the recent increase in online recruitment and virtual interviews. Unfortunately, there is limited guidance on how to address imposter participants in an equitable, trauma-informed way. To bridge this gap, we share imposter participant red flags, challenges, and a protocol that provides questions to ask and possible activities to engage in throughout the research process from conceptualization through findings dissemination. We ground this guidance in examples from our recent study with LGBTQ+ (e.g., lesbian, gay, bisexual, transgender, queer) survivors of sexual and intimate partner violence
Glycolytic regulation of cell rearrangement in angiogenesis
During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases
Role of glutamine synthetase in angiogenesis beyond glutamine synthesis
Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation
Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability
Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7–54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of “perceptual noise.” This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population
Elephants and optimality again: SA-OT accounts for pronoun resolution in child language
Children display a surprising delay in correctly resolving pronouns, while they employ Chomsky’s binding principles correctly in production and in resolving reflexives. We account for the mistakes as performance errors that are predicted by an Optimality Theoretical model implemented using simulated annealing. Our experiments suggest three novel explanations of the facts. Additionally, the Optimality Theory-Harmony Grammar connection is also explored: the behaviour of the HG-based performance model converges to the OTmodel if the base of the exponential weights grow large
P2.04-76 Tumor Mutational Burden by TSO500 Next Generation Sequencing Panel and Clinical Outcome in Non-Small Cell Lung Cancer
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