NF-κB-inducing kinase regulates selected gene expression in the Nod2 signaling pathway

The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-κB pathway. It has been suggested through indirect studies that NF-κB-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK(−/−) mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense

Moderation of neoclassical impurity accumulation in high temperature plasmas of helical devices

Achieving impurity and helium ash control is a crucial issue in the path towards fusion-grade magnetic confinement devices, and this is particularly the case of helical reactors, whose low-collisionality ion-root operation scenarios usually display a negative radial electric field which is expected to cause inwards impurity pinch. In this work we discuss, based on experimental measurements and standard predictions of neoclassical theory, how plasmas of very low ion collisionality, similar to those observed in the impurity hole of the large helical device (Yoshinuma et al and The LHD Experimental Group 2009 Nucl. Fusion 49 062002, Ida et al and The LHD Experimental Group 2009 Phys. Plasmas 16 056111 and Yokoyama et al and LHD Experimental Group 2002 Nucl. Fusion 42 143), can be an exception to this general rule, and how a negative radial electric field can coexist with an outward impurity flux. This interpretation is supported by comparison with documented discharges available in the International Stellarator-Heliotron Profile Database, and it can be extrapolated to show that achievement of high ion temperature in the core of helical devices is not fundamentally incompatible with low core impurity content

Surgical removal of amyloid-laden lymph nodes: a possible therapeutic approach in a primary systemic AL amyloidosis patient with focal lymphadenopathy

We report a patient with primary systemic AL amyloidosis who suffered from remarkable bilateral cervical lymphadenopathy. Intensive chemotherapies, including two cycles of high-dose melphalan with autologous peripheral blood stem cell transplantation, were insufficiently effective for both the lymphadenopathy and amyloidogenic IgG lambda lambda-type M-protein in serum, but the patient showed complete haematological remission after extensive surgical removal of enlarged lymph nodes that had massive depositions of lambda lambda-type immunoglobulin light chain-derived amyloid. Lymphadenectomy may be a possible therapeutic approach with regard to both cosmetic and haematological aspects in primary systemic AL amyloidosis patients with focal lymphadenopathy.ArticleAMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS. 18(2):79-82 (2011)journal articl

Extended capability of the integrated transport analysis suite, TASK3D-a, for LHD experiment

The integrated transport analysis suite, TASK3D-a (Analysis), has been developed to be capable for routine whole-discharge analyses of plasmas confined in three-dimensional (3D) magnetic configurations such as the LHD. The routine dynamic energy balance analysis for NBI-heated plasmas was made possible in the first version released in September 2012. The suite has been further extended through implementing additional modules for neoclassical transport and ECH deposition for 3D configurations. A module has also been added for creating systematic data for the International Stellarator–Heliotron Confinement and Profile Database. Improvement of neutral beam injection modules for multiple-ion species plasmas and loose coupling with a large-simulation code are also highlights of recent developments

Development and application of a ray-tracing code integrating with 3D equilibrium mapping in LHD ECH experiments

The central electron temperature has successfully reached up to 7.5 keV in large helical device(LHD) plasmas with a central high-ion temperature of 5 keV and a central electron density of1.3×1019 m−3. This result was obtained by heating with a newly-installed 154 GHz gyrotronand also the optimisation of injection geometry in electron cyclotron heating (ECH). Theoptimisation was carried out by using the ray-tracing code ‘LHDGauss’, which was upgradedto include the rapid post-processing three-dimensional (3D) equilibrium mapping obtainedfrom experiments. For ray-tracing calculations, LHDGauss can automatically read the relevantdata registered in the LHD database after a discharge, such as ECH injection settings (e.g.Gaussian beam parameters, target positions, polarisation and ECH power) and Thomsonscattering diagnostic data along with the 3D equilibrium mapping data. The equilibrium mapof the electron density and temperature profiles are then extrapolated into the region outsidethe last closed flux surface. Mode purity, or the ratio between the ordinary mode and theextraordinary mode, is obtained by calculating the 1D full-wave equation along the directionof the rays from the antenna to the absorption target point. Using the virtual magnetic fluxsurfaces, the effects of the modelled density profiles and the magnetic shear at the peripheralregion with a given polarisation are taken into account. Power deposition profiles calculatedfor each Thomson scattering measurement timing are registered in the LHD database. Theadjustment of the injection settings for the desired deposition profile from the feedbackprovided on a shot-by-shot basis resulted in an effective experimental procedure

Stable sustainment of plasmas with electron internal transport barrier by ECH in the LHD

The long pulse experiments in the Large Helical Device has made progress in sustainment of improved confinement states. It was found that steady-state sustainment of the plasmas with improved confinement at the core region, that is, electron internal transport barrier (e-ITB), was achieved with no significant difficulty. Sustainment of a plasma having e-ITB with the line average electron density ne_ave of 1.1 × 1019 m−3 and the central electron temperature Te0 of ∼3.5 keV for longer than 5 min only with 340 kW ECH power was successfully demonstrated

The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia

<p>Abstract</p> <p>Background</p> <p>We have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE ₂and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE ₂is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE ₂in TLR4-/- mice to see if PGE ₂bypasses the protection from colitis-associated tumorigenesis.</p> <p>Method</p> <p>Mouse colitis-associated neoplasia was induced by azoxymethane (AOM) injection followed by two cycles of dextran sodium sulfate (DSS) treatment. Two different doses of PGE ₂(high dose group, 200 μg, n = 8; and low dose group, 100 μg, n = 6) were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE ₂during DSS treatment (200 μg, n = 5). Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.</p> <p>Results</p> <p>In control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13) than in TLR4-/- mice (n = 7). High dose but not low dose PGE ₂treatment caused an increase in epithelial proliferation. 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 ± 0.2). By contrast, 75.0% (tumors/animal: 1.5 ± 1.2, P < 0.05) of the high dose group and 33.3% (tumors/animal: 0.3 ± 0.5) of the low dose group developed dysplasia in TLR4-/- mice. Tumor size was also increased by high dose PGE ₂treatment. Endogenous prostanoid synthesis was differentially affected by PGE ₂treatment during acute and recovery phases of colitis. Exogenous administration of PGE ₂increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE ₂treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.</p> <p>Conclusions</p> <p>These results highlight the importance of PGE ₂as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis.</p

Isotope effects on energy, particle transport and turbulence in electron cyclotron resonant heating plasma of the Large Helical Device

Positive isotope effects have been found in electron cyclotron resonant heating plasma of the Large Helical Device (LHD). The global energy confinement time (τE) in deuterium (D) plasma is 16% better than in hydrogen (H) plasma for the same line-averaged density and absorption power. The power balance analyses showed a clear reduction in ion energy transport, while electron energy transport does not change dramatically. The global particle confinement time (τp) is degraded in D plasma; τp in D plasma is 20% worse than in H plasma for the same line-averaged density and absorption power. The difference in the density profile was not due to the neutral or impurity sources, but rather was due to the difference in the transport. Ion scale turbulence levels show isotope effects. The core turbulence (ρ  =  0.5–0.8) level is higher in D plasma than in H plasma in the low collisionality regime and is lower in D plasma than in H plasma. The density gradient and collisionality play a role in the core turbulence level