T-Cell responses in individuals infected with Zika virus and in those vaccinated against dengue virus

Background: The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT. Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE

Effet du chlore sur la colonisation bactérienne d'un réseau expérimental de distribution d'eau

La contamination bactérienne de la phase eau d'un réseau de distribution résulte d'une multiplication des bactéries sur les parois des canalisations d'eau (biofilms) suivie de leur arrachage et de leur transport dans le flux circulant. Ce travail met en évidence l'effet du chlore, d'une part, sur la formation des biofilms et, d'autre part, sur des biofilms déjà constitués. Des éprouvettes de matériaux neufs introduites dans des eaux présentant des concentrations en chlore total variant de 2,4 à 0,02 mg/l et véhiculant entre 0,5 x 106 et 5 x 105 cellules bactériennes/mi (dont 1 à 10 % de bactéries cultivables) sont rapidement colonisées (106 à 108 cellules/cm2). L'effet du chlore est sensible sur les cellules totales pour des concentrations de l'ordre de 1 à 2,4 mg/l. Sur les bactéries cultivables, un ralentissement de la croissance du biofilm est observé dès 0,3 mg/1 de chlore total. Par contre, des résiduels de 0,02 ou 0,05 mg/l sont sans effet sur la cinétique de formation des biofilms. Des résiduels moyens de chlore total compris entre 2,3 et 3,4 mg/l appliqués en continu pendant 14 jours sur un biofilm constitué d'environ 8,7 x 106 cellules par cm2 (1,7 % de bactéries cultivables), entraînent l'élimination d'environ 90 % des bactéries fixées (abattement d'1 logarithme) durant les premiers jours d'exposition. L'altération du biofilm exposé à un résiduel de chlore total de l'ordre de 1,3 mg/l est identique, mais toutefois plus étalée dans le temps. Ces essais réalisés sur des éprouvettes de PVC, PE et mortier de ciment n'ont pas permis la mise en évidence de comportements différents de ces 3 supports..Bacterial accumulation in drinking water systems results both of cell deposition on the pipe walls and attached bacteria growth. The presence of a complex biofilm (cells embedded in a matrix of exopolymers) leads to a continuous contamination of the water phase resulting from the erosion of the attached growing biomass. Then, many tentatives to lmit the formation of such a biofilm have been suggested as the removal of biodegradable organic matter fram water or as the application of disinfectant. However, the efficiency of chlorination of the distribution system is debatable. Indeed, adhesion is often described as a factor of protection of attached bacteria which counterbalances the expected effect of disinfectant. Then, the aim of this experimental work is using a model distribution system to evaluate (i) the kinetics of biofilm accumulation on coupons of new materials (Polyvinyl chlorure : PVC, polyethylene : PE, cement) disposed in a constantly chlorinated system (residual total chlorine from 0.021o 2.4 mg. l-1), (ii) the effect of chlorination on previously accumulated biofilms.The industrial pilot plant used in this study is comprised of five loops serially disposed (fig. 1). From previous study of simulation, one may assume that each loop works like a perfectly mixed reactor when the whole pilot plant is equivalent to an infinite tubular reactor with high axial dispersion coefficient. During the experiment, the pilot was continuously fed with finished drinking water front the surface water treatment plant of city of Nancy (i.e. natural finished water with its own chlorine demand, organic nutrients and heterotrophic bacteria).Total number of cells (epifluorescence counts) and heterotrophic plate count bacteria (15 days of incubation at 20 °C) were enumerated both in the water and, after sonication, on the surface of the coupons of tested materials.The first experimentations show that chlorine slows clown the kinetic of deposition of bacteria onto the pipe wall but never prohibits biofilm formation. When the drinking waters carried from 2.4 to 0.02 mg.1-1 of chlorine and from 0.5 to 5 x 105 ml-1 bacterial cells, biofilm is observed after 24 hours of immersion of the coupons with at least 101 to 106 bacteria/cm2. Respectively, the deposition or/and growth rates of total cells are drastically affected only for chlorine residual as high as 1 to 2.4 mg. 1-1. The number of heterotrophic plate count of the biofilm is affected with lower chlorine residual (around 0.3 mg.1-1) but residual concentration as low as 0.05 mg.1-1 are ineffective.The tentatives carried out in the second experience on preformed biofilms (2 months old biofilms, 8.7 x 106 cells/cm2) show that the continuous application of 2.3 to 3.4 mg. 1-1 of residual chlorine for 14 days, leads to the removal of only 90 % of attached total cells without modifications of the proportion of attached alive bacteria (around 1.7 %) into the biofitm. In other wards, a highly chlorinated networks shows at minima 106 attached cells/cm2. Its generally takes several days to reply to the chlorine demand of the system and to have a quasi steady state reactor in terms of residual chlorine.These assays carried out with three types of coupons (PVC, PE, cement lined cast iron) did not show any difference between the tested materials.The limited efficiency of chlorine against the biofilm can be explained by transfert limitations within the visquous layer, high consumption of chlorine by the biopolymers of the attached matrix (proteins...) or low sensitivity to the disinfectant of the slow growing attached bacteria. Then chlorination is really not a panacea in biofilm war but has to be applied in combination with other methods as biodegradable organic matter removal, hydraulic regime improvement..

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections

In Situ mechanical effects of a specific neurodynamic mobilization of the superficial fibular nerve: A cadaveric study

Context: A specific neurodynamic mobilization for the superficial fibular nerve (SFN) has been suggested in the reference literature for manual therapists to evaluate nerve mechanosensitivity in patients. However, no biomechanical studies examined the ability of this technique to produce nerve strain. Therefore, mechanical specificity of this technique is not yet established. Objective: The aim of our study was to test whether this examination and treatment technique was producing nerve strain in the fresh frozen cadaver and the contribution of each motion to total longitudinal strain. Design: Quantitative original research, controlled laboratory study Methods: A differential variable reluctance transducer was inserted in ten SFN from six fresh cadavers to measure strain during the mobilization. A specific sequence of plantar flexion (PF), ankle inversion (INV), straight leg raise (SLR) position and 30{degree sign} of hip adduction (ADD) was applied to the lower limb. The mobilization was repeated at 0°, 30°, 60° and 90° of Straight Leg Raise (SLR) position to measure the impact of hip flexion position. Findings: Compared to a resting position, this neurodynamic mobilization produced a significant amount of strain in the SFN (7.93% ± 0.51 P < 0.001). PF (59.34% ± 25.82) and INV (32.80% ± 21.41) accounted for the biggest proportion of total strain during the mobilization. No significant difference was reported between different hip flexion positions. Hip ADD did not significantly contribute to final strain (0.39% ± 10.42 P> 0,05) although high subject variability exists. Conclusion: Ankle motions should be considered the most important during neurodynamic assessment of the SFN for distal entrapment. These results suggest that this technique produces sufficient strain in the SFN and could therefore be evaluated In Vivo for correlation with mechanosensitivit

Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

Hunger Artists: Yeast Adapted to Carbon Limitation Show Trade-Offs under Carbon Sufficiency

As organisms adaptively evolve to a new environment, selection results in the improvement of certain traits, bringing about an increase in fitness. Trade-offs may result from this process if function in other traits is reduced in alternative environments either by the adaptive mutations themselves or by the accumulation of neutral mutations elsewhere in the genome. Though the cost of adaptation has long been a fundamental premise in evolutionary biology, the existence of and molecular basis for trade-offs in alternative environments are not well-established. Here, we show that yeast evolved under aerobic glucose limitation show surprisingly few trade-offs when cultured in other carbon-limited environments, under either aerobic or anaerobic conditions. However, while adaptive clones consistently outperform their common ancestor under carbon limiting conditions, in some cases they perform less well than their ancestor in aerobic, carbon-rich environments, indicating that trade-offs can appear when resources are non-limiting. To more deeply understand how adaptation to one condition affects performance in others, we determined steady-state transcript abundance of adaptive clones grown under diverse conditions and performed whole-genome sequencing to identify mutations that distinguish them from one another and from their common ancestor. We identified mutations in genes involved in glucose sensing, signaling, and transport, which, when considered in the context of the expression data, help explain their adaptation to carbon poor environments. However, different sets of mutations in each independently evolved clone indicate that multiple mutational paths lead to the adaptive phenotype. We conclude that yeasts that evolve high fitness under one resource-limiting condition also become more fit under other resource-limiting conditions, but may pay a fitness cost when those same resources are abundant

Pathways to functional outcomes in schizophrenia spectrum disorders: Meta-analysis of social cognitive and neurocognitive predictors

The current meta-analysis explored relationships between functional outcomes in schizophrenia spectrum disorders and different domains of neurocognition and social cognition. Literature searches were conducted in PsycINFO, PubMed, and ProQuest to identify articles reporting correlations between cognition domains and functional outcomes. Of 1361 articles identified, 166 met all inclusion criteria (12,868 participants; 518 correlations). Fifty-three random-effects meta-analyses yielded mean correlation estimates for relationships between neurocognition and social cognition and functional outcomes. Overall, associations between social cognition and neurocognition, and functional outcomes demonstrated significant small-to-medium effect sizes. Social cognition explained more unique variance in functioning than neurocognition (7.3% vs. 4.4%; 9.2% total average variance). Social cognition also mediated the relationship between neurocognition and functional outcomes. A significant proportion of the variance in the relationships between cognition and functional outcomes remained unexplained. These findings suggest that integrated interventions targeting both neurocognition and social cognition may optimally improve functional outcomes. Standardized measurement of cognition and functioning, longitudinal studies, and tests of additional moderators (e.g., first episode samples) in future research were identified as important future directions

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production

The RV144 Thai phase III clinical trial’s canarypox–protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration