Immune dysregulation as a cause of autoinflammation in fragile X premutation carriers: link between FMRI CGG repeat number and decreased cytokine responses.

BackgroundIncreased rates of autoinflammatory and autoimmune disorders have been observed in female premutation carriers of CGG repeat expansion alleles of between 55-200 repeats in the fragile X mental retardation 1 (FMR1) gene. To determine whether an abnormal immune profile was present at a cellular level that may predispose female carriers to autoinflammatory conditions, we investigated dynamic cytokine production following stimulation of blood cells. In addition, splenocyte responses were examined in an FMR1 CGG knock-in mouse model of the fragile X premutation.MethodsHuman monocyte and peripheral blood leukocytes (PBLs) were isolated from the blood of 36 female FMR1 premutation carriers and 15 age-matched controls. Cells were cultured with media alone, LPS or PHA. In the animal model, splenocytes were isolated from 32 CGG knock-in mice and 32 wild type littermates. Splenocytes were cultured with media alone or LPS or PMA/Ionomycin. Concentrations of cytokines (GM-CSF, IL-1β, IL-6, IL-10, IL-13, IL-17, IFNγ, TNFα, and MCP-1) were determined from the supernatants of cellular cultures via Luminex multiplex assay. Additionally, phenotypic cellular markers were assessed on cells isolated from human subjects via flow cytometry.ResultsWe found decreases in cytokine production in human premutation carriers as well as in the FMR1 knock-in mice when compared with controls. Levels of cytokines were found to be associated with CGG repeat length in both human and mouse. Furthermore, T cells from human premutation carriers showed decreases in cell surface markers of activation when compared with controls.ConclusionsIn this study, FMR1 CGG repeat expansions are associated with decreased immune responses and immune dysregulation in both humans and mice. Deficits in immune responses in female premutation carriers may lead to increased susceptibility to autoimmunity and further research is warranted to determine the link between FMR1 CGG repeat lengths and onset of autoinflammatory conditions

Unilateral Hemiparesis with Thoracic Epidural in an Adolescent

Objective. Unilateral sensory and motor blockade is known to occur with epidural anesthesia but is rarely reported in children. The differential diagnosis should include the presence of a midline epidural septum. Case Report. We describe a case of a 16-year-old adolescent who developed repeated complete unilateral extensive epidural sensory and motor blockade with Horner's syndrome after thoracic epidural catheter placement. This unusual presentation of complete hemibody neural blockade has not been reported in the pediatric population. Maneuvers to improve contralateral uniform neural blockade were unsuccessful. An epidurogram was performed to ascertain the correct location of the catheter within the epidural space and presence of sagittal compartmentalization. Conclusion. This case report highlights a less frequently reported reason for unilateral sensory and motor blockade with epidural anesthesia in children. The presence of a midline epidural septum should be considered in the differential diagnosis of unilateral epidural blockade

Role of bound pairs in the optical properties of highly excited semiconductors: a self consistent ladder approximation approach

Presence of bound pairs (excitons) in a low-temperature electron-hole plasma is accounted for by including correlation between fermions at the ladder level. Using a simplified one-dimensional model with on-site Coulomb interaction, we calculate the one-particle self-energies, chemical potential, and optical response. The results are compared to those obtained in the Born approximation, which does not account for bound pairs. In the self-consistent ladder approximation the self-energy and spectral function show a characteristic correlation peak at the exciton energy for low temperature and density. In this regime the Born approximation overestimates the chemical potential. Provided the appropriate vertex correction in the interaction with the photon is included, both ladder and Born approximations reproduce the excitonic and free pair optical absorption at low density, and the disappearance of the exciton absorption peak at larger density. However, lineshapes and energy shifts with density of the absorption and photoluminescence peaks are drastically different. In particular, the photoluminescence emission peak is much more stable in the ladder approximation. At low temperature and density a sizeable optical gain is produced in both approximations just below the excitonic peak, however this gain shows unphysical features in the Born approximation. We conclude that at low density and temperature it is fundamental to take into account the existence of bound pairs in the electron-hole plasma for the calculation of its optical and thermodynamic properties. Other approximations that fail to do so are intrinsically unphysical in this regime, and for example are not suitable to address the problem of excitonic lasing.Comment: 14 pages, 12 figure

Relaxation bottleneck and its suppression in semiconductor microcavities

A polariton relaxation bottleneck is observed in angle-resolved measurements of photoluminescence emission from a semiconductor microcavity. For low power laser excitation, low k polariton states are found to have a very small population relative to those at high k. The bottleneck is found to be strongly suppressed at higher powers in the regime of superlinear emission of the lower polariton states. Evidence for the important role of carrier-carrier scattering in suppression of the bottleneck is presented

Photoelasticity of sodium silicate glass from first principles

Based on density-functional perturbation theory we have computed the photoelastic tensor of a model of sodium silicate glass of composition (Na$_2$O)$_{0.25}$(SiO$_2$)$_{0.75}$ (NS3). The model (containig 84 atoms) is obtained by quenching from the melt in combined classical and Car-Parrinello molecular dynamics simulations. The calculated photoelastic coefficients are in good agreement with experimental data. In particular, the calculation reproduces quantitatively the decrease of the photoelastic response induced by the insertion of Na, as measured experimentally. The extension to NS3 of a phenomenological model developed in a previous work for pure a-SiO$_2$ indicates that the modulation upon strain of other structural parameters besides the SiOSi angles must be invoked to explain the change in the photoelstic response induced by Na

Time resolved scattering relaxation mechanisms of microcavity polaritons

We study the polariton relaxation dynamics for different scattering mechanisms as: Phonon and electron scattering procesess. The relaxation polariton is obtained at very short times by solving the Boltzman equation. Instead of the well-known relaxation process by phonons, we show that the bottleneck effect relaxes to the ground state more efficiently at low pump power intensity when the electron relaxation process is included. In this way, we clearly demonstrate that different relaxation times exist, for which any of these two mechanism is more efficient to relax the polariton population to the ground state.Comment: 10 eps figure