Effects of fluoride on primary cultured haemocytes from the marine gastropod Haliotis tuberculata

International audienceAs a consequence of human's activities, fluoride concentration in many aquatic ecosystems is significantly increasing. Nevertheless, little is known about fluoride toxicity to aquatic life. In this study the effect of exposure to different concentrations of sodium fluoride (2, 10, 50, 250 and 1,250 μg mL −1) during 24 h on primary cultured haemocytes of the gastropod Haliotis tuberculata was realized. Results indicate no significant effect of NaF on cell viability, Lysosomal membrane stability, phagocytosis and ROS production at concentrations of 2, 10, 50 and 250 μg mL −1. Nevertheless, lysosomal membrane alterations, a decrease of phagocytosis and morphological changes of H. tuberculata haemocytes were observed at concentration of 1,250 µg mL −1 NaF suggesting a potential impact of NaF at high concentration in the environment

Optimization of the Touchscreen-Based Visuomotor Conditional Learning Task in Mice

The translational gap between animal models and clinical trials is a longstanding, yet largely unresolved, limitation in the study of cognition. This discrepancy is largely due to the differences in how cognition is assessed in animal models compared to those in clinical populations. In the stimulus-response (S-R) learning literature, for example, the techniques used to assess the acquisition of habitual behaviour differ greatly across species, leading to poor cross-species translation and often conflicting results. As a result, we set out to optimize a S-R learning task in mice using the touchscreen-based operant technologies. Similar to human studies, this touchscreen technique encourages animals to respond to visual stimuli displayed on a touchscreen according to a specific rule. Allowing for very similar, if not identical, cognitive assays in mice and men, this technique promotes high translational potential and a high degree of standardisation. Originally developed for rats, the Visuomotor Conditional Learning (VMCL) task encourages animals to learn arbitrary associations between visual stimuli and motor responses. In naïve C57BL/6 mice, we sought to optimize VMCL task parameters to promote better and more efficient responding, identifying the length of inter-trial intervals and the limited hold period as two potential candidates. The validation of this task will provide a novel means through which to study the neural correlates of S-R learning, and its use in conjunction with fiber photometry recordings may be provided

Biological laterality and peripheral nerve DTI metrics

BACKGROUND AND PURPOSE: Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular). MATERIALS AND METHODS: We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed. RESULTS: A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles. CONCLUSION: For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients’ recovery and how we forecast pain chronification

A two-phase flow model to simulate mold filling and saturation in Resin Transfer Molding

The final publication is available at Springer via http://dx.doi.org/10.1007/s12289-015-1225-zThis paper addresses the numerical simulation of void formation and transport during mold filling in Resin Transfer Molding (RTM). The saturation equation, based on a two-phase flow model resin/air, is coupled with Darcy s law and mass conservation to simulate the unsaturated filling flow that takes place in a RTM mold when resin is injected through the fiber bed. These equations lead to a system composed of an advection diffusion equation for saturation including capillary effects and an elliptic equation for pressure taking into account the effect of air residual saturation. The model introduces the relative permeability as a function of resin saturation. When capillary effects are omitted, the hyperbolic nature of the saturation equation and its strong coupling with Darcy equation through relative permeability represent a challenging numerical issue. The combination of the constitutive physical laws relating permeability to saturation with the coupled system of the pressure and saturation equations allows predicting the saturation profiles. The model was validated by comparison with experimental data obtained for a fiberglass reinforcement injected in a RTM mold at constant flow rate. The saturation measured as a function of time during the resin impregnation of the fiber bed compared very well with numerical predictions.The authors acknowledge financial support of the Spanish Government (Projects DPI2010-20333 and DPI2013-44903-R-AR), of the National Science and Research Council of Canada (NSERC) and of the Canada Reseach Chair (CRC) program.Gascón Martínez, ML.; García Manrique, JA.; Lebel, F.; Ruiz, E.; Trochu, F. (2016). A two-phase flow model to simulate mold filling and saturation in Resin Transfer Molding. International Journal of Material Forming. 9(2):229-239. doi:10.1007/s12289-015-1225-zS22923992Patel N, Lee LJ (1996) Modeling of void formation and removal in liquid composite molding. Part I: wettability analysis. Polym Compos 17(1):96–103Ruiz E, Achim V, Soukane S, Trochu F, Bréard J (2006) Optimization of injection flow rate to minimize micro/macro-voids formation in resin transfer molded composites. Compos Sci Technol 66(3–4):475–486Trochu F, Ruiz E, Achim V, Soukane S (2006) Advanced numerical simulation of liquid composite molding for process analysis and optimization. Compos A: Appl Sci Manuf 37(6):890–902Park CH, Lee W (2011) Modeling void formation and unsaturated flow in liquid composite molding processes: a survey and review. J Reinf Plast Compos 30(11):957–977Pillai KM (2004) Modeling the unsaturated flow in liquid composite molding processes: a review and some thoughts. 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DTI and MTR Measures of Nerve Fiber Integrity in Pediatric Patients With Ankle Injury

Acute peripheral nerve injury can lead to chronic neuropathic pain. Having a standardized, non-invasive method to evaluate pathological changes in a nerve following nerve injury would help with diagnostic and therapeutic assessments or interventions. The accurate evaluation of nerve fiber integrity after injury may provide insight into the extent of pathology and a patient's level of self-reported pain. The aim of this investigation was to evaluate the extent to which peripheral nerve integrity could be evaluated in an acute ankle injury cohort and how markers of nerve fiber integrity correlate with self-reported pain levels in afferent nerves. We recruited 39 pediatric participants with clinically defined neuropathic pain within 3 months of an ankle injury and 16 healthy controls. Participants underwent peripheral nerve MRI using diffusion tensor (DTI) and magnetization transfer imaging (MTI) of their injured and non-injured ankles. The imaging window was focused on the branching point of the sciatic nerve into the tibial and fibular division. Each participant completed the Pain Detection Questionnaire (PDQ). Findings demonstrated group differences in DTI and MTI in the sciatic, tibial and fibular nerve in the injured ankle relative to healthy control and contralateral non-injured nerve fibers. Only AD and RD from the injured fibular nerve correlated with PDQ scores which coincides with the inversion-dominant nature of this particular ankle injuruy cohort. Exploratory analyses highlight the potential remodeling stages of nerve injury from neuropathic pain. Future research should emphasize sub-acute time frames of injury to capture post-injury inflammation and nerve fiber recovery

Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression

Preclinical and clinical studies suggest that inflammation and vascular dysfunction contribute to the pathogenesis of major depressive disorder (MDD). Chronic social stress alters blood–brain barrier (BBB) integrity through loss of tight junction protein claudin-5 (cldn5) in male mice, promoting passage of circulating proinflammatory cytokines and depression-like behaviors. This effect is prominent within the nucleus accumbens, a brain region associated with mood regulation; however, the mechanisms involved are unclear. Moreover, compensatory responses leading to proper behavioral strategies and active resilience are unknown. Here we identify active molecular changes within the BBB associated with stress resilience that might serve a protective role for the neurovasculature. We also confirm the relevance of such changes to human depression and antidepressant treatment. We show that permissive epigenetic regulation of cldn5 expression and low endothelium expression of repressive cldn5-related transcription factor foxo1 are associated with stress resilience. Regionand endothelial cell-specific whole transcriptomic analyses revealed molecular signatures associated with stress vulnerability vs. resilience. We identified proinflammatory TNFα/NFκB signaling and hdac1 as mediators of stress susceptibility. Pharmacological inhibition of stress-induced increase in hdac1 activity rescued cldn5 expression in the NAc and promoted resilience. Importantly, we confirmed changes in HDAC1 expression in the NAc of depressed patients without antidepressant treatment in line with CLDN5 loss. Conversely, many of these deleterious CLDN5-related molecular changes were reduced in postmortem NAc from antidepressanttreated subjects. These findings reinforce the importance of considering stress-induced neurovascular pathology in depression and provide therapeutic targets to treat this mood disorder and promote resilience