66 research outputs found

    Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

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    BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

    Effect of thermal processing on the tribology of nanocrystalline Ni/TiO2 coatings

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    yesThe tribological performance of a nanocrystalline coating is heavily influenced by its composition, morphology, and microstructural characteristics. This research work describes the effect of heat treatment temperature on the microstructural, morphological, and mechanical behavior of nanocrystalline Ni/TiO2 coatings produced by electrophoresis. The surface morphology and coating cross section were characterized by scanning electron microscopy (SEM). The composition of coatings and the percentage of TiO2 nanoparticles incorporated in the Ni matrix were studied and estimated by using an energy-dispersive spectroscopic (EDS) analysis, while x-ray diffractometry (XRD) was used to investigate the effect of heat treatment temperature on phase structure. The results showed agglomeration of TiO2 nanoparticles on the surface of the coating. The high hardness and wear resistance recorded for the as-deposited coating was attributed to the uniform distribution of TiO2 nanoparticle clusters throughout the cross section of the coating. Heat treatment of the Ni/TiO2 coatings to temperatures above 200 °C led to significant grain growth that changed the surface morphology of the coating and reduced the strengthening effects of the nanoparticles, thus causing a reduction in the hardness and wear resistance of the coatings

    Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

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    Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems

    Biocontrol Potential of Forest Tree Endophytes

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    Repurposing of approved cardiovascular drugs

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    Failure analysis of cracked NLG brackets

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    Two cracked NLG brackets; one in finished condition and the other in semi-finished condition, were sent to the laboratory for analysis. Cracks were noticed in the components during dye penetrant inspection. It was established that the cracks were resulted during heat treatment of the semi-finished components. Hence, study was undertaken to establish first whether or not there were any problems in the material or in heat treatment procedure. Microstructural and fractographic examination confirmed that there were no abnormalities in the material. Based on the microstructural study, the possibility of overheating during heat treatment was also ruled out. However, analysis of the failure, in general, indicated that most probably, the cracking of the NLG brackets occurred due to differential stresses that got developed in different sections of the components during quenching process. Because of the shape, varying thickness and extra material left in the component after semi-finishing operation, some of the fillet regions were found to be vulnerable for crack generation during quenching operation. Analysis also shows that such heat treatment cracking in the NLG brackets in its present form is probably unavoidable. In view of this, it is recommended that suitable modification be made in the design so that the fabrication problems encountered currently can be avoided
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