14 research outputs found
Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation
BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation
Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?
AbstractBackgroundSmall-for-size syndrome (SFSS) is a feared complication of extended liver resection and partial liver transplantation. Swine models of extended hepatectomy have been developed for studying SFSS and its different treatment options. Although portal inflow modulation (PIM) by splenectomy or splenic artery ligation (SAL) has been proposed in humans to prevent SFSS, such procedures have not yet been evaluated in swine.ObjectivesThe present study was designed to evaluate modifications in splanchnic haemodynamics yielded by extended hepatectomy with and without PIM in swine.MethodsNineteen animals underwent 70% hepatectomy (H70, n = 7), 90% hepatectomy (H90, n = 7) or sham laparotomy (H0, n = 5). Haemodynamic measurements were performed at baseline, after hepatectomy and after PIM by SAL and splenectomy.ResultsPortal vein flow increased after both H70 (273 ml/min/100 g versus 123 ml/min/100 g; P = 0.016) and H90 (543 ml/min/100 g versus 124 ml/min/100 g; P = 0.031), but the hepatic venous pressure gradient (HVPG) increased only after H90 (10.0 mmHg versus 3.7 mmHg; P = 0.016). Hepatic artery flow did not significantly decrease after either H70 or H90. In all three groups, neither splenectomy nor SAL induced any changes in splanchnic haemodynamics.ConclusionsSubtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy
Modular slowing of resting-state dynamic functional connectivity as a marker of cognitive dysfunction induced by sleep deprivation
International audienceDynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks. In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks-including Rapid Visual Processing (RVP, assessing sustained visual attention)-and dFC speed quantified at the level of functional sub-networks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module
Experimental and natural evidence of SARS-CoV- 2-infection-induced activation of type I interferon responses
Type I interferons (IFNs) are our first line of defense against virus infection.
Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit
IFN responses. Emerging data also suggest that timing and extent of IFN production
is associated withmanifestation of COVID-19 severity. In spite of progress in
understanding how SARS-CoV-2 activates antiviral responses, mechanistic
studies into wild-type SARS-CoV-2-mediated induction and inhibition of human
type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection
induces a type I IFN response in vitro and inmoderate cases of COVID-19. In vitro
stimulation of type I IFN expression and signaling in human airway epithelial cells
is associated with activation of canonical transcriptions factors, and SARS-CoV-2
is unable to inhibit exogenous induction of these responses. Furthermore, we
show that physiological levels of IFNa detected in patients with moderate
COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.Medicine, Faculty ofNon UBCMedicine, Department ofRespiratory Medicine, Division ofReviewedFacultyResearcherPostdoctoralGraduat
External validation of prognostic scores for COVID-19: a multicenter cohort study of patients hospitalized in Greater Paris University Hospitals
International audiencePurposeThe Coronavirus disease 2019 (COVID-19) has led to an unparalleled influx of patients. Prognostic scores could help optimizing healthcare delivery, but most of them have not been comprehensively validated. We aim to externally validate existing prognostic scores for COVID-19.MethodsWe used “COVID-19 Evidence Alerts” (McMaster University) to retrieve high-quality prognostic scores predicting death or intensive care unit (ICU) transfer from routinely collected data. We studied their accuracy in a retrospective multicenter cohort of adult patients hospitalized for COVID-19 from January 2020 to April 2021 in the Greater Paris University Hospitals. Areas under the receiver operating characteristic curves (AUC) were computed for the prediction of the original outcome, 30-day in-hospital mortality and the composite of 30-day in-hospital mortality or ICU transfer.ResultsWe included 14,343 consecutive patients, 2583 (18%) died and 5067 (35%) died or were transferred to the ICU. We examined 274 studies and found 32 scores meeting the inclusion criteria: 19 had a significantly lower AUC in our cohort than in previously published validation studies for the original outcome; 25 performed better to predict in-hospital mortality than the composite of in-hospital mortality or ICU transfer; 7 had an AUC > 0.75 to predict in-hospital mortality; 2 had an AUC > 0.70 to predict the composite outcome.ConclusionSeven prognostic scores were fairly accurate to predict death in hospitalized COVID-19 patients. The 4C Mortality Score and the ABCS stand out because they performed as well in our cohort and their initial validation cohort, during the first epidemic wave and subsequent waves, and in younger and older patients
Obesity Doubles Mortality in Patients Hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 in Paris Hospitals, France: A Cohort Study on 5,795 Patients
International audienc