Analyzing symmetry breaking within a chaotic quantum system via Bayesian inference

Bayesian inference is applied to the level fluctuations of two coupled microwave billiards in order to extract the coupling strength. The coupled resonators provide a model of a chaotic quantum system containing two coupled symmetry classes of levels. The number variance is used to quantify the level fluctuations as a function of the coupling and to construct the conditional probability distribution of the data. The prior distribution of the coupling parameter is obtained from an invariance argument on the entropy of the posterior distribution.Comment: Example from chaotic dynamics. 8 pages, 7 figures. Submitted to PR

Bayesian Model Selection Applied to the Analysis of Fluorescence Correlation Spectroscopy Data of Fluorescent Proteins in Vitro and in Vivo

Fluorescence correlation spectroscopy (FCS) is a powerful technique to investigate molecular dynamics with single molecule sensitivity. In particular, in the life sciences it has found widespread application using fluorescent proteins as molecularly specific labels. However, FCS data analysis and interpretation using fluorescent proteins remains challenging due to typically low signal-to-noise ratio of FCS data and correlated noise in autocorrelated data sets. As a result, naive fitting procedures that ignore these important issues typically provide similarly good fits for multiple competing models without clear distinction of which model is preferred given the signal-to-noise ratio present in the data. Recently, we introduced a Bayesian model selection procedure to overcome this issue with FCS data analysis. The method accounts for the highly correlated noise that is present in FCS data sets and additionally penalizes model complexity to prevent over interpretation of FCS data. Here, we apply this procedure to evaluate FCS data from fluorescent proteins assayed in vitro and in vivo. Consistent with previous work, we demonstrate that model selection is strongly dependent on the signal-to-noise ratio of the measurement, namely, excitation intensity and measurement time, and is sensitive to saturation artifacts. Under fixed, low intensity excitation conditions, physical transport models can unambiguously be identified. However, at excitation intensities that are considered moderate in many studies, unwanted artifacts are introduced that result in nonphysical models to be preferred. We also determined the appropriate fitting models of a GFP tagged secreted signaling protein, Wnt3, in live zebrafish embryos, which is necessary for the investigation of Wnt3 expression and secretion in development. Bayes model selection therefore provides a robust procedure to determine appropriate transport and photophysical models for fluorescent proteins when appropriate models are provided, to help detect and eliminate experimental artifacts in solution, cells, and in living organisms.National Science Foundation (U.S.). Physics of Living Systems ProgramNational Institute of Mental Health (U.S.) (Award U01MH106011

Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency

International audienceIn immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk

Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis.

International audienceThe IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33

Wealth is health: High economic status in Cameroon correlates with protective gear use in traffic injuries and improved clinical outcomes

IntroductionAfrica is the least motorized populated continent, yet it experiences the highest traffic fatality rate. Despite laws mandating helmet and seatbelt use, data on protective gear use among Cameroonian road traffic injury (RTI) patients remains sparse.MethodsWe extracted Cameroon Trauma Registry data prospectively collected from 10 hospitals during July 2022 to December 2023. Protective gear users wore helmets in motorcycle and seatbelts/car seats in vehicle crashes. We categorized patients into five economic clusters based on ownership of durable goods using parallel distance matrix computation. We analyzed associations between continuous variables with Wilcoxon rank-sum and categorical variables with χ 2 and multivariate logistic regression. Our primary outcome was in-hospital death or major disability at discharge.ResultsAmong 3,554 RTI patients, 303 (9%) used protective gear. A larger proportion of patients who did not use protective gear were designated as majorly disabled or dead (20% vs. 16%, p < 0.001). The greatest percentage of protective gear users belonged to the richest cluster, while the poorest cluster patients comprised the smallest proportion of protective gear users (13% vs. 3%, p < 0.001). The richest cluster demonstrated the smallest percentage of major disability or death (13%), while the poorest cluster had the greatest percentage (28%, p < 0.001). When controlling for age, protective gear use, and injury severity, the three poorest clusters showed the greatest odds of major disability or death (cluster 3: adjusted odds ratio [AOR], 2.34; 95% confidence interval [CI], 1.58-3.46; cluster 4: AOR, 2.09; 95% CI, 1.59-2.74; cluster 5: AOR, 2.38; 95% CI, 1.24-4.58).ConclusionGreater economic status is associated with increased protective gear use during RTIs in Cameroon. Despite suffering the most severe outcomes, the poorest patients remain less likely to use protective gear. Enforcement of protective gear laws and economic incentives such as price subsidies for helmets and seatbelts would particularly benefit the most vulnerable population.Level of evidencePrognostic and Epidemiological; Level IV

Capturing and Quantifying Particle Transcytosis with Microphysiological Intestine-on-Chip Models

Understanding the intestinal transport of particles is critical in several fields ranging from optimizing drug delivery systems to capturing health risks from the increased presence of nano- and micro-sized particles in human environment. While Caco-2 cell monolayers grown on permeable supports are the traditional in vitro model used to probe intestinal absorption of dis-solved molecules, they fail to recapitulate the transcytotic activity of polar-ized enterocytes. Here, an intestine-on-chip model is combined with in silico modeling to demonstrate that the rate of particle transcytosis is ≈350× higher across Caco-2 cell monolayers exposed to fluid shear stress compared to Caco-2 cells in standard “static” configuration. This relates to profound phe-notypical alterations and highly polarized state of cells grown under mechan-ical stimulation and it is shown that transcytosis in the microphysiological model is energy-dependent and involves both clathrin and macropinocytosis mediated endocytic pathways. Finally, it is demonstrated that the increased rate of transcytosis through cells exposed to flow is explained by a higher rate of internal particle transport (i.e., vesicular cellular trafficking and baso-lateral exocytosis), rather than a change in apical uptake (i.e., binding and endocytosis). Taken together, the findings have important implications for addressing research questions concerning intestinal transport of engineered and environmental particles.Ludivine C. Delon, Matthew Faria, Zhengyang Jia, Stuart Johnston, Rachel Gibson, Clive A. Prestidge, and Benjamin Thierr