Brain imaging of the rejection process in patient 3 and its reversion under treatment.

<p>Magnetic resonance imaging and metabolic activity using ¹⁸F-deoxyglucose before surgery (T0), during the rejection process (T1) and after 6 months of reinstated immunosuppressive treatment (T2) are shown separately (upper and middle panel, respectively), then co-registered (lower panel). The white arrow indicates the right striatum. The false colour scale shows levels of metabolic activities from lowest (min) to highest (max).</p

Production of IL-1β, TNF-α and IL-6 by PBMCs of 2 Schnitzler syndrome (SS-1 for patient 1 and SS-2 for patient2) patients and 6 healthy subjects (HSs) in different conditions of culture.

<p>(i) baseline: no stimulation condition of PBMCs; (ii) LPS stimulation (100 pg/ml); (iii) LPS stimulation (100 pg/ml) plus 500 ng/ml anakinra <i>in vitro.</i> Release of cytokine was evaluated in the supernatants collected at both 6 hours (middle gray histograms) and 16 hours (dark gray histograms) of culture conditions. Results are expressed as the mean of triplicate measures of cytokine concentration (± SD). In the SS patients, cytokine release was measured before and 1 month after <i>in vivo</i> anakinra treatment. In HSs, cytokine release is expressed as the mean of values (+/− SD) obtained in 6 independent evaluations.</p

On an efficient multiple time step Monte Carlo simulation of the SABR model

textabstractIn this paper, we will present a multiple time step Monte Carlo simulation technique for pricing options under the Stochastic Alpha Beta Rho model. The proposed method is an extension of the one time step Monte Carlo method that we proposed in an accompanying paper Leitao et al. [Appl. Math. Comput. 2017, 293, 461–479], for pricing European options in the context of the model calibration. A highly efficient method results, with many very interesting and nontrivial components, like Fourier inversion for the sum of log-normals, stochastic collocation, Gumbel copula, correlation approximation, that are not yet seen in combination within a Monte Carlo simulation. The present multiple time step Monte Carlo method is especially useful for long-term options and for exotic options

Effect of rapamycin on the expression of MDSCs specific genes by MDSCs purified from adipose tissue and liver (22 weeks post-injection).

<p>(<b>A</b>) RT-qPCR analysis of MDSCs purified from VWAT, after 22 injections (Rapa: ▪, Ve: □): Expression levels of <i>Arg1</i>, <i>Nos2</i> and <i>C/EBP-β</i> (normalized to <i>Eef2</i> expression) (n = 5 mice per group). (<b>B</b>) RT-qPCR analysis of MDSCs purified from the liver, after 22 injections (Rapa: ▪, Ve: □): Expression levels of <i>Arg1</i>, <i>Nos2</i> and <i>C/EBP-β</i> (normalized to <i>Eef2</i> expression) (n = 5 mice per group). (<b>A</b>–<b>B</b>) Data are expressed as mean ± S.E.M. of 5 mice per group. ^##<i>p<</i>0.01, ^###<i>p<</i>0.001.</p

Beneficial Metabolic Effects of Rapamycin Are Associated with Enhanced Regulatory Cells in Diet-Induced Obese Mice

<div><p>The “mechanistic target of rapamycin” (mTOR) is a central controller of growth, proliferation and/or motility of various cell-types ranging from adipocytes to immune cells, thereby linking metabolism and immunity. mTOR signaling is overactivated in obesity, promoting inflammation and insulin resistance. Therefore, great interest exists in the development of mTOR inhibitors as therapeutic drugs for obesity or diabetes. However, despite a plethora of studies characterizing the metabolic consequences of mTOR inhibition in rodent models, its impact on immune changes associated with the obese condition has never been questioned so far. To address this, we used a mouse model of high-fat diet (HFD)-fed mice with and without pharmacologic mTOR inhibition by rapamycin. Rapamycin was weekly administrated to HFD-fed C57BL/6 mice for 22 weeks. Metabolic effects were determined by glucose and insulin tolerance tests and by indirect calorimetry measures of energy expenditure. Inflammatory response and immune cell populations were characterized in blood, adipose tissue and liver. In parallel, the activities of both mTOR complexes (<i>e. g.</i> mTORC1 and mTORC2) were determined in adipose tissue, muscle and liver. We show that rapamycin-treated mice are leaner, have enhanced energy expenditure and are protected against insulin resistance. These beneficial metabolic effects of rapamycin were associated to significant changes of the inflammatory profiles of both adipose tissue and liver. Importantly, immune cells with regulatory functions such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were increased in adipose tissue. These rapamycin-triggered metabolic and immune effects resulted from mTORC1 inhibition whilst mTORC2 activity was intact. Taken together, our results reinforce the notion that controlling immune regulatory cells in metabolic tissues is crucial to maintain a proper metabolic status and, more generally, comfort the need to search for novel pharmacological inhibitors of the mTOR signaling pathway to prevent and/or treat metabolic diseases.</p></div