Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release

Allergy is becoming a rapidly increasing problem worldwide, and in vitro models are frequently used to study the mechanisms behind the different types of allergic response. The dendritic cell (DC)\u2013T-cell model can be used to study sensitization. However, lipopolysaccharide (LPS) is often used to maturate the DCs, but it gives rise to a DC1 phenotype, whereas Th2-driven inflammatory diseases such as allergy are characterized by the involvement of the DC2 phenotype. Our aim was to create a DC2\u2013T-cell human model (human moDC2s) to study in vitro sensitization and validate the model using polyunsaturated fatty acids (PUFAs) that were previously shown to have immunomodulatory properties. We found that the generated DC2s expressed OX40L and drove naive T-cells into IL-13 production of CD4+ effector T-cells. In line with in vivo findings, n 123 long-chain (LC)PUFA docosahexaenoic acid (DHA) effectively decreased the DC2's surface expression of OX40L, as well as the IL-12p40 and IL-23 cytokine production by DC2s and subsequently lowered IL-13 production by DC2-induced effector T-cells. Similar cytokine production effects were found with eicosapentaenoic acid (EPA) and arachidonic acid (AA), whereas linoleic acid (LA) increased OX40L surface expression and subsequent T-cell-derived IL-13/IFN\u3b3 ratios, suggesting an increased risk of allergy development. Altogether, these data show that human moDC2s are able to induce Th2-type IL-13 secretion by T-cell differentiated in the presence of these DC2s and that this model can be differentially modulated by PUFAs. These results are in line with previous in vivo studies using PUFAs, indicating that this model may be of use to predict in vivo outcomes

Critical State Flux Penetration and Linear Microwave Vortex Response in YBa_2Cu_3O_{7-x} Films

The vortex contribution to the dc field (H) dependent microwave surface impedance Z_s = R_s+iX_s of YBa_2Cu_3O_{7-x} thin films was measured using suspended patterned resonators. Z_s(H) is shown to be a direct measure of the flux density B(H) enabling a very precise test of models of flux penetration. Three regimes of field-dependent behavior were observed: (1) Initial flux penetration occurs on very low field scales H_i(4.2K) 100Oe, (2) At moderate fields the flux penetration into the virgin state is in excellent agreement with calculations based upon the field-induced Bean critical state for thin film geometry, parametrized by a field scale H_s(4.2K) J_c*d 0.5T, (3) for very high fields H >>H_s, the flux density is uniform and the measurements enable direct determination of vortex parameters such as pinning force constants \alpha_p and vortex viscosity \eta. However hysteresis loops are in disagreement with the thin film Bean model, and instead are governed by the low field scale H_i, rather than by H_s. Geometric barriers are insufficient to account for the observed results.Comment: 20 pages, LaTeX type, Uses REVTeX style files, Submitted to Physical Review B, 600 dpi PostScript file with high resolution figures available at http://sagar.physics.neu.edu/preprints.htm

Melatonin treatment in children with therapy-resistant monosymptomatic nocturnal enuresis

Objective: To evaluate the effects of exogenous melatonin on the frequency of wet nights, on the sleep-wake cycle, and on the melatonin profile in children with therapy-resistant MNE. Patients and methods: 24 patients were included. Patients had to maintain a diary including time of sleep and arousal, and whether they had a dry or a wet bed in the morning. We measured baseline melatonin profiles in saliva. Hereafter, patients were randomized to synthetic melatonin or placebo. After 3 and 6 months we evaluated the frequency of enuresis and the melatonin profiles. Results: 11 patients were randomized to melatonin, 13 to placebo. We evaluated melatonin profiles of 7 patients in the melatonin group and of 8 in the placebo group. We observed a change in profile in the melatonin group, but we did not observe a difference in the sleep-wake cycle or the frequency of wet nights in either group. Conclusion: This is the first time exogenous melatonin has been evaluated in the treatment of MNE. Although we observed a change in melatonin profile after the use of exogenous melatonin, we did not observe a change in enuresis frequency or in the sleep-wake cycle of this select group of patients. (C) 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved

Microwave Current Imaging in Passive HTS Components by Low-Temperature Laser Scanning Microscopy (LTLSM)

We have used the LTLSM technique for a spatially resolved investigation of the microwave transport properties, nonlinearities and material inhomogeneities in an operating coplanar waveguide YBa_2Cu_3O_{7-\delta} (YBCO) microwave resonator on an LaAlO_3 (LAO) substrate. The influence of twin-domain blocks, in-plane rotated grains, and micro-cracks in the YBCO film on the nonuniform rf current distribution were measured with a micrometer-scale spatial resolution. The impact of the peaked edge currents and rf field penetration into weak links on the linear device performance were studied as well. The LTLSM capabilities and its future potential for non-destructive characterization of the microwave properties of superconducting circuits are discussed.Comment: 8 pages, 9 figures, 2-column format, presented at High Temperature Superconductors in High Frequency Fields 2004, Journal of Superconductivity (in press

Freely decaying weak turbulence for sea surface gravity waves

We study numerically the generation of power laws in the framework of weak turbulence theory for surface gravity waves in deep water. Starting from a random wave field, we let the system evolve numerically according to the nonlinear Euler equations for gravity waves in infinitely deep water. In agreement with the theory of Zakharov and Filonenko, we find the formation of a power spectrum characterized by a power law of the form of $|{\bf k}|^{-2.5}$.Comment: 4 pages, 3 figure

Thin superconducting disk with B-dependent Jc: Flux and current distributions

The critical state in a superconducting thin circular disk with an arbitrary magnetic field dependence of the critical sheet current, Jc(B), is analyzed. With an applied field Ba perpendicular to the disk, a set of coupled integral equations for the flux and current distributions is derived. The equations are solved numerically, and flux and current profiles are presented graphically for several commonly used Jc(B) dependences. It is shown that for small Ba the flux penetration depth can be described by an effective Bean model with a renormalized Jc entering the leading term. We argue that these results are qualitatively correct for thin superconductors of any shape. The results contrast the parallel geometry behavior, where at small Ba the B-dependence of the critical current can be ignored.Comment: RevTeX, 7 pages including 8 figure

Dopaminergic Neuronal Loss and Dopamine-Dependent Locomotor Defects in Fbxo7-Deficient Zebrafish

Recessive mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, a Mendelian form of early-onset, levodopa-responsive parkinsonism with severe loss of nigrostriatal dopaminergic neurons. However, the function of the protein encoded by FBXO7, and the pathogenesis of PARK15 remain unknown. No animal models of this disease exist. Here, we report the generation of a vertebrate model of PARK15 in zebrafish. We first show that the zebrafish Fbxo7 homolog protein (zFbxo7) is expressed abundantly in the normal zebrafish brain. Next, we used two zFbxo7-specific morpholinos (targeting protein translation and mRNA splicing, respectively), to knock down the zFbxo7 expression. The injection of either of these zFbxo7-specific morpholinos in the fish embryos induced a marked decrease in the zFbxo7 protein expression, and a range of developmental defects. Furthermore, whole-mount in situ mRNA hybridization showed abnormal patterning and significant decrease in the number of diencephalic tyrosine hydroxylase-expressing neurons, corresponding to the human nigrostriatal or ventral tegmental dopaminergic neurons. Of note, the number of the dopamine transporter-expressing neurons was much more severely depleted, suggesting dopaminergic dysfunctions earlier and larger than those due to neuronal loss. Last, the zFbxo7 morphants displayed severe locomotor disturbances (bradykinesia), which were dramatically improved by the dopaminergic agonist apomorphine. The severity of these morphological and behavioral abnormalities correlated with the severity of zFbxo7 protein deficiency. Moreover, the effects of the co-injection of zFbxo7- and p53-specific morpholinos were similar to those obtained with zFbxo7-specific morpholinos alone, supporting further the contention that the observed phenotypes were specifically due to the knock down of zFbxo7. In conclusion, this novel vertebrate model reproduces pathologic and behavioral hallmarks of human parkinsonism (dopaminergic neuronal loss and dopamine-dependent bradykinesia), representing therefore a valid tool for investigating the mechanisms of selective dopaminergic neuronal death, and screening for modifier genes and therapeutic compounds

Интеллектуалы в дискурсе власти постсовременности

Background: It is suggested that allergic immune activation, combined with a genetic predisposition, may contribute to the expression of aberrant social behaviour relevant to autism. We have previously shown that a food allergic response reduced social behaviour in mice, which was associated with altered dopaminergic activity in brain regions relevant for social and emotional behaviour. Dietary fatty acid composition has been shown to affect both the immune system and neurological processes and may therefore contribute to the prevention of food allergy-induced abnormalities in social behaviour. Method: The aim of this study was to assess whether dietary supplementation with fish oil rich in long chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA) prevents food allergy-induced abnormalities in social behaviour and associated deficits of the dopaminergic system in the prefrontal cortex of whey-sensitised mice. Results: The n-3 LCPUFA-enriched fish oil diet decreased the acute allergic skin response and was able to prevent the disturbance in social behaviour of whey-sensitised mice. N-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation in the brain and restored levels of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA) in the prefrontal cortex of allergic mice. Moreover, reduced levels of 5-HIAA, metabolite of serotonin, in intestines of allergic mice was also restored by the n-3 LCPUFA-enriched diet. Conclusion: In addition to its effects on the allergic skin response, n-3 LCPUFA restored allergy-induced deficits in social behaviour and in prefrontal dopamine and metabolite levels. Therefore, n-3 LCPUFA may exert its beneficial effect on behaviour via modulation of the dopaminergic system in the prefrontal cortex and may therefore be an interesting target in the use of dietary interventions for immune-mediated psychiatric disorders such as ASD