Research on communication between glia and neurons has increased in the past decade. The onset of neuropathic pain, a major clinical problem that is not resolved by available therapeutics, involves activation of spinal cord glia through the release of proinflammatory cytokines in acute animal models of neuropathic pain. Here, we demonstrate for the first time that the spinal action of the proinflammatory cytokine, interleukin 1 (IL-1) is involved in maintaining persistent (2 months) allodynia induced by chronic-constriction injury (CCI). The anti-inflammatory cytokine IL-10 can suppress proinflammatory cytokines and spinal cord glial amplification of pain. Given that IL-1 is a key mediator of neuropathic pain, developing a clinically viable means of long-term delivery of IL-10 to the spinal cord is desirable. High doses of intrathecal IL-10-gene therapy using naked plasmid DNA (free pDNA-IL-10) is effective, but the dose required limits its potential clinical utility. Here we show that intrathecal gene therapy for neuropathic pain is improved sufficiently using two, distinct synthetic polymers, poly(lactic-co-glycolic) and polyethylenimine, that substantially lower doses of pDNA-IL-10 are effective. In conclusion, synthetic polymers used as i.t. gene-delivery systems are well-tolerated and improve the long-duration efficacy of pDNA-IL-10 gene therapy.
Nematic liquid crystals (LC) were exposed to isolated DNA molecules extended on a surface that imparted a negligible influence on the LC orientation. Although single-stranded DNA aligned the LC in the extension direction, double-stranded DNA (dsDNA) caused alignment at an oblique angle, providing a characteristic response to the chiral dsDNA helix that was readily observed optically. The intrinsic amplification due to LC orientational correlations enabled a macroscopic visible response to a single molecule of extended dsDNA.
Diffusiophoresis is the migration of a colloidal particle through a viscous fluid, caused by a gradient in concentration of some molecular solute; a long-range physical interaction between the particle and solute molecules is required. In the case of a charged particle and an ionic solute (e.g., table salt, NaCl), previous studies have predicted and experimentally verified the speed for very low salt concentrations at which the salt solution behaves ideally. The current study presents a study of diffusiophoresis at much higher salt concentrations (approaching the solubility limit). At such large salt concentrations, electrostatic interactions are almost completely screened, thus eliminating the long-range interaction required for diffusiophoresis; moreover, the high volume fraction occupied by ions makes the solution highly nonideal. Diffusiophoretic speeds were found to be measurable, albeit much smaller than for the same gradient at low salt concentrations.
Alkylsilane self-assembled monolayers (SAMs) on oxide substrates are commonly used as liquid crystal (LC) alignment layers. We have studied the effects of alkyl chain length, photolytic degradation, and mechanical rubbing on polar and azimuthal LC anchoring. Both gradient surfaces (fabricated using photolytic degradation of C18 SAMs) and unirradiated SAMs composed of short alkyl chains show abrupt transitions from homeotropic to tilted alignment as a function of degradation or chain length. In both cases, the transition from homeotropic to tilted anchoring corresponds to increasing wettability of the SAM surfaces. However, there is an offset in the critical contact angle for the transition on gradient vs unirradiated SAMs, suggesting that layer thickness is more relevant than wettability for LC alignment. Mechanical rubbing can induce azimuthal alignment along the rubbing direction for alignment layers sufficiently near the homeotropic-to-planar transition. Notably, mechanical rubbing causes a small but significant shift in the homeotropic-to-tilted transition, e.g., unrubbed C5 SAMs induce homeotropic anchoring, but the same surface after rubbing induces LC pretilt.
A photoisomerizable fatty acid (containing an azobenzene unit) was dissolved in a nematic liquid crystal (LC), and adsorbed at the LC/water interface, influencing the anchoring of the LC material. Reorientation of the LC phase was observed upon exposure of the system to different irradiation wavelengths. Homeotropic, tilted, and planar anchoring were all observed under various thermodynamic and illumination conditions. Lateral coexistence between regions displaying different anchoring was often observed, as were dynamic and reversible transitions between the various states. These observations suggest that adsorbed monolayers of the azobenzene-fatty acid (probably in equilibrium with the same surfactant in solution) display a rich binary phase diagram, where the relative fractions of cis and trans isomers are determined by the photostationary state associated with the illumination wavelength. The morphology of these phase diagrams has been determined as a function of three variables-bulk concentration, temperature, and composition (cis-trans ratio) of the dissolved surfactant-and six distinct interfacial phases were identified, including five condensed phases and a dilute interfacial vapor phase. This phase diagram is distinct from the behavior of Langmuir monolayers of the same amphiphile at the air/water interface, which exhibits only two condensed phases.
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