Modeling CD4+ T cells dynamics in HIV-infected patients receiving repeated cycles of exogenous Interleukin 7

Combination Antiretroviral Therapy (cART) succeeds to control viral replication in most HIV infected patients. This is normally followed by a reconstitution of the CD4$^+$ T cells pool; however, this does not happen for a substantial proportion of patients. For these patients, an immunotherapy based on injections of Interleukin 7 (IL-7) has been recently proposed as a co-adjutant treatment in the hope of obtaining long-term reconstitution of the T cells pool. Several questions arise as to the long-term efficiency of this treatment and the best protocol to apply. We develop a model based on a system of ordinary differential equations and a statistical model of variability and measurement. We can estimate key parameters of this model using the data from INSPIRE, INSPIRE 2 $\&$ INSPIRE 3 trials. In all three studies, cycles of three injections have been administered; in the last two studies, for the first time, repeated cycles of exogenous IL-7 have been administered. Our aim was to estimate the possible different effects of successive injections in a cycle, to estimate the effect of repeated cycles and to assess different protocols. The use of dynamical models together with our complex statistical approach allow us to analyze major biological questions. We found a strong effect of IL-7 injections on the proliferation rate; however, the effect of the third injection of the cycle appears to be much weaker than the first ones. Also, despite a slightly weaker effect of repeated cycles with respect to the initial one, our simulations show the ability of this treatment of maintaining adequate CD4$^+$ T cells count for years. We were also able to compare different protocols, showing that cycles of two injections should be sufficient in most cases. %Finally, we also explore the possibility of adaptive protocols

Temperature dependence of second-order nonlinear relaxation of a poled chromophore doped sol-gel material

International audienceSecond-order optical nonlinearity relaxations of hybrid inorganic/organic sol-gel films doped with poled Disperse Red 1 chromophores were measured by second harmonic generation at several temperatures. The decay curves were fitted to biexponentials and Ko¨hlrausch, Williams, and Watts ~KWW! stretched exponentials. It can be concluded that the KWW model well describes chromophore thermal reorientation in hybrid sol-gel materials, as is known for all-organic polymers. Using the Arrhenius law, the activation energy of the reorientation process has been determined to be about 50 or 70 kcal mol21. A stability of roughly a decade has been extrapolated at room temperature. Another experiment at room temperature gave an estimation of the stability that was found to be in qualitative agreement. It is shown that poled chromophore-doped sol-gel materials have the potential to be stable enough for applications in telecommunication device

Two Photon Absorption in Chromophore Doped Solid Matrices

Over the past decades organic materials have shown an important potential for applications in the field of nonlinear optics. Two-photon absorbing materials can be optically addressed in three dimensions of space, which make them unique for many new applications, including 3D displays, optical memories, bio-sensors, etc. Fluorescent organic chromophores can be synthesized with structures especially optimized for this nonlinear optical property. Yet, for some applications, they have to be incorporated in solid state matrices. We especially investigate hybrid organic/inorganic doped matrices synthesized by solgel process. However , the linear transmission for such molecules is often significantly less than unity. Two-photon absorption (TPA) offers the advantage of very high transmission at low incident intensity, while being sensitive to high intensity laser pulses. Our aim is to record a 3D layered pattern of optical memory inside the sample by the use of the picosecond pulsed ND3+:YAG laser at 532nm, or 1064nm

Pericardial effusion as the only manifestation of infection with Francisella tularensis: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Francisella tularensis</it>, a facultative intracellular Gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. <it>F. tularensis </it>is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. However, cross-reactions may occur. Western blotting allows the correct diagnosis.</p> <p>Case presentation</p> <p>A non-smoking 53-year-old woman was admitted to hospital with a large posterior pericardial effusion. Serological tests showed a seroconversion in antibody titers to <it>F. tularensis </it>(IgG titer = 400) and <it>Legionella pneumophila </it>(IgG titer = 512). <it>F. tularensis </it>was identified by Western immunoblotting following cross-adsorption. The patient reported close contact with rabbits 2 weeks prior to the beginning of symptoms of pericarditis.</p> <p>Conclusion</p> <p>We report a rare case of pericardial effusion as the only manifestation of infection by <it>F. tularensis</it>. The etiological diagnosis is based on serology. Western blotting and cross-adsorption allow differential diagnosis.</p

CFTR Depletion Results in Changes in Fatty Acid Composition and Promotes Lipogenesis in Intestinal Caco 2/15 Cells

Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The mechanism(s) underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role.The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7)/16:0, was significantly higher in knockdown cells and consistent with the striking elevation of the n-7 FA family. When incubated with [14C]-oleic acid, CFTR-depleted cells were capable of quick incorporation and export to the medium concomitantly with the high protein expression of L-FABP known to promote intracellular FA trafficking. Accordingly, lipoprotein vehicles (CM, VLDL, LDL and HDL), isolated from CFTR knockdown cells, exhibited higher levels of radiolabeled FA. Moreover, in the presence of [14C]-acetate, knockdown cells exhibited enhanced secretion of newly synthesized phospholipids, triglycerides, cholesteryl esters and free FA, thereby suggesting a stimulation of the lipogenic pathway. Conformably, gene expression of SREBP-1c, a key lipogenic transcription factor, was increased while protein expression of the phosphorylated and inactive form of acetylCoA carboxylase was reduced, confirming lipogenesis induction. Finally, CFTR-depleted cells exhibited lower gene expression of transcription factors (PPARalpha, LXRalpha, LXRbeta and RXRalpha).Collectively, our results indicate that CFTR depletion may disrupt FA homeostasis in intestinal cells through alterations in FA uptake and transport combined with stimulation of lipogenesis that occurs by an LXR/RXR-independent mechanism. These findings exclude a contributing role of CFTR in CF-associated fat malabsorption

Assessment of the MERS-CoV epidemic situation in the Middle East region

The appearance of a novel coronavirus named Middle East (ME) Respiratory Syndrome Coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME region and importations in Europe to assess transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and underascertainment. Maximum likelihood estimates for the ME region indicate the occurrence of a subcritical epidemic (R=0.50, 95% confidence interval (CI) 0.30-0.77) associated with a 0.28 (95% CI 0.12-0.85) daily rate of sporadic introductions. Infections in the region appear to be mainly dominated by zoonotic/environmental transmissions, with possible underascertainment (95% CI of estimated to observed sporadic cases in the range 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from the region indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit underascertainment, and calls for increased alertness in high-risk areas worldwide.Comment: in press on Eurosurveillance, 16 pages, 3 figure

Stable photorefractive memory effect in sol-gel materials

International audienceWe report on the synthesis and the optical characterization of a photorefractive sol-gel material which contains nonlinear azo chromophore and carbazole charge transporting molecules. Both of these functional groups are covalently attached to the silica based backbone. Thin sol-gel films exhibit stable optically nonlinear properties: the electro-optic coefficient r13 measured at 633 nm is found to be 17 pm/V one day after corona poling and 15 pm/V after three weeks and over a period of several months. Photorefractivity is demonstrated by two beam coupling experiments without external applied electric field. Sol-gel films present a stable photorefractive memory effect with a net internal gain of 200 cm-

Non-Dipping Blood Pressure Profile in Narcolepsy with Cataplexy

BACKGROUND: Patients with narcolepsy-cataplexy (NC) mostly exhibit undetectable hypocretin levels. Hypocretin system is one of the key players in the complex interaction between sleep and the cardiovascular system. We tested the hypothesis that hypocretin deficiency affects cardiovascular risk factors by measuring nighttime and daytime ambulatory blood pressure (BP) and the night-to-day BP ratio as well as endothelial dysfunction by the digital pulse amplitude response in drug-free patients with NC compared to controls. METHODOLOGY: Sleep, clinical and biological cardiovascular risk factors, fingertip peripheral arterial tonometry, and 24-hour ambulatory BP monitoring were recorded in 50 drug-free patients with NC and 42 healthy control subjects, except for BP monitoring available in all controls but in 36 patients with NC. PRINCIPAL FINDINGS: More patients than controls were smokers, obese and with dyslipidemia. One-third of patients with NC were "non-dippers" (defined as <10% drop in BP during sleep) compared to only 3% of controls. The diastolic non-dipper BP profile had up to 12-fold higher odds of being associated with NC. We noted negative correlations between mean diastolic BP fall during night, REM sleep percentage and number of sleep onset REM periods, and a positive correlation with mean sleep latency on the MSLT. The digital pulse amplitude response measured by fingertip was similar between NC and controls. CONCLUSION: We found a high percentage of non-dippers in patients with NC with association with REM sleep dysregulation. The blunted sleep-related BP dip in NC may be of clinical relevance, as it may indicate increased risk for cardiovascular events

DR1 doped sol-gel planar waveguides for nonlinear devices operating at telecommunications wavelengths

International audienceWe report on linear and nonlinear optical properties of Disperse Red 1-doped solgel waveguides. The refractive-index and optical-propagation losses of the guiding layer were measured between 0.756 mm and 1.64 mm. The spectral broadening of the chromophore charge-transfer transition in the visible is modeled with a Voigt-profile function. In the telecommunications window the attenuation is dominated by the overtones of the O--H bonds vibration bands. The nonlinear optical coefficients were measured at different poling strengths with the Maker-fringe method. The nonlinear coefficient d33 was found to be 4.5 pm V21 at 1.58 mm for a poling field of 60 Vmm21

A Re-Examination of Hebbian-Covariance Rules and Spike Timing-Dependent Plasticity in Cat Visual Cortex in vivo

Spike timing-dependent plasticity (STDP) is considered as an ubiquitous rule for associative plasticity in cortical networks in vitro. However, limited supporting evidence for its functional role has been provided in vivo. In particular, there are very few studies demonstrating the co-occurrence of synaptic efficiency changes and alteration of sensory responses in adult cortex during Hebbian or STDP protocols. We addressed this issue by reviewing and comparing the functional effects of two types of cellular conditioning in cat visual cortex. The first one, referred to as the “covariance” protocol, obeys a generalized Hebbian framework, by imposing, for different stimuli, supervised positive and negative changes in covariance between postsynaptic and presynaptic activity rates. The second protocol, based on intracellular recordings, replicated in vivo variants of the theta-burst paradigm (TBS), proven successful in inducing long-term potentiation in vitro. Since it was shown to impose a precise correlation delay between the electrically activated thalamic input and the TBS-induced postsynaptic spike, this protocol can be seen as a probe of causal (“pre-before-post”) STDP. By choosing a thalamic region where the visual field representation was in retinotopic overlap with the intracellularly recorded cortical receptive field as the afferent site for supervised electrical stimulation, this protocol allowed to look for possible correlates between STDP and functional reorganization of the conditioned cortical receptive field. The rate-based “covariance protocol” induced significant and large amplitude changes in receptive field properties, in both kitten and adult V1 cortex. The TBS STDP-like protocol produced in the adult significant changes in the synaptic gain of the electrically activated thalamic pathway, but the statistical significance of the functional correlates was detectable mostly at the population level. Comparison of our observations with the literature leads us to re-examine the experimental status of spike timing-dependent potentiation in adult cortex. We propose the existence of a correlation-based threshold in vivo, limiting the expression of STDP-induced changes outside the critical period, and which accounts for the stability of synaptic weights during sensory cortical processing in the absence of attention or reward-gated supervision