TNFAIP3, a negative regulator of the TLR signaling pathway, is a potential predictive biomarker of response to antidepressant treatment in major depressive disorder

AbstractInflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants. Positive regulators of the TLR4 pathway, including Pellino 1, TRAF6 and IRAK1, were also investigated. Among all patients, MyD88s, and TNFAIP3 mRNAs were expressed at lower levels in PBMCs from patients with MDD. Multiple linear regression analyses revealed that TNFAIP3 mRNA expression before treatment was inversely correlated with severity of depression and effectively predicted improvement in HAMD-17 scores. Among 79 treatment-completers, only TNFAIP3 mRNA was significantly increased by treatment with antidepressants for 4 weeks. Treatment of human monocytes (THP-1) and mouse microglia (SIM-A9) cell lines with fluoxetine significantly increased TNFAIP3 mRNA expression and suppressed IL-6 levels. The suppressive effect of fluoxetine on IL-6 was attenuated by knockdown of TNFAIP3 expression. These findings suggest that both dysfunction of the negative regulatory system in patients with MDD and antidepressant treatment exert anti-inflammatory effects, at least in part through increased expression of the TNFAIP3 gene. They also indicate that modulating expression of the TNFAIP3 gene to rebalance TLR-mediated inflammatory signaling may be potential therapeutic strategy for treating MDD

Internal evaluation of a physically-based distributed model using data from a Mediterranean mountain catchment

An evaluation of the performance of a physically-based distributed model of a small Mediterennean mountain catchment is presented. This was carried out using hydrological response data, including measurements of runoff, soil moisture, phreactic surface level and actual evapotranspiration. A-priori model parameterisation was based as far as possible on property data measured in the catchment. Limited model calibration was required to identify an appropriate value for terms controlling water loss to a deeper regional aquifer. The model provided good results for an initial calibration period, when judge in terms of catchment discharge. However, model performance for runoff declined substantially when evaluated againts a consecutive, rather drier, period of data. Evaluation against other catchment responses allowed identification of the problems responsible for the observed lack of model robustness in flow simulation. In particular, it was shown that an incorrect parameterisation of the soil water was preventing adequate representation of drainage from soils during hydrogeraph recessions. This excess moisture was then being removed via an overestimation of evapotranspiration. It also appeared that the model underestimated canopy interception. The results presented here suggest that model evaluation against catchment scale variables summarising its water balance can be of great use in identifying problems with model parameterisation, even for distributed models. Evaluation using spatially distributed data yielded less useful information on model performance, owing to the relative sparseness of data points, and problems of mismatch of scale between the measurement and the model grid.This work was carried out as part of project VAHMPIRE (Validating Hydrological Models using Process Studies and Internal Data from Research Basins: tools for assessing the hydrological impacts of environmental change), which was funded by the European Commission Framework IV Environment and Climate Program (Contract No. ENV4- CT95-0134). Simulations were carried out on a UNIX workstation funded jointly by UK Nirex Ltd. and NERC grant GR3/ E0009.Peer Reviewe

Readout-segmented echo-planar imaging in diffusion-weighted mr imaging in breast cancer: comparison with single-shot echo-planar imaging in image quality

Objective: The purpose of this study was to compare the image quality of standard single-shot echo-planar imaging (ss-EPI) and that of readout-segmented EPI (rs-EPI) in patients with breast cancer. Materials and Methods: Seventy-one patients with 74 breast cancers underwent both ss-EPI and rs-EPI. For qualitative comparison of image quality, three readers independently assessed the two sets of diffusion-weighted (DW) images. To evaluate geometric distortion, a comparison was made between lesion lengths derived from contrast enhanced MR (CE-MR) images and those obtained from the corresponding DW images. For assessment of image parameters, signal-to-noise ratio (SNR), lesion contrast, and contrast-to-noise ratio (CNR) were calculated. Results: The rs-EPI was superior to ss-EPI in most criteria regarding the qualitative image quality. Anatomical structure distinction, delineation of the lesion, ghosting artifact, and overall image quality were significantly better in rs-EPI. Regarding the geometric distortion, lesion length on ss-EPI was significantly different from that of CE-MR, whereas there were no significant differences between CE-MR and rs-EPI. The rs-EPI was superior to ss-EPI in SNR and CNR. Conclusion: Readout-segmented EPI is superior to ss-EPI in the aspect of image quality in DW MR imaging of the breast

Long-term outcome of Bartter syndrome in 54 patients: A multicenter study in Korea

IntroductionBartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce.MethodsWe retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea.ResultsAll patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0–271) months, and their median follow-up was 8 (range, 0.5–27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had SLC12A1 gene mutations, 1 had KCNJ1 gene mutations, 33 had CLCNKB gene mutations, and 1 had BSND mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, n = 4; CKD G5, n = 2].ConclusionBS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3–G5

Shape-shifting nanoparticles on a perovskite oxide for highly stable and active heterogeneous catalysis

Controlling the geometric shape of nano-catalysts plays a key role in maximizing unique properties of the materials. Although shape control of nanoparticles is well known by various preparation methods, still there is no clear case for exsolution. Here we show that the shape of embedded Ni nanoparticles can be changed on exsolution process, by controlling reduction temperature and time. To elucidate and generalize the shape-shifting, we develop a model which describes the equilibrium shape of nanoparticles on support thermodynamically. Our results suggest that there is a thermodynamic driving force for the exsolved nanoparticle to be stabilized into faceted shape with low surface/interface energy, during the particle growth. Through catalytic activity testing, the improved durability of shape-shifted Ni catalysts is confirmed on dry-reforming condition over 390 h, resulting from enhanced interface stability and cocking resistance. This provides theoretical and experimental framework for the shape control of exsolved particle on oxide support, but also for the design of unique catalyst with high stability and reactivity

Functional MR Imaging of Psychogenic Amnesia: A Case Report

We present here a case in which functional MR imaging (fMRI) was done for a patient who developed retrograde psychogenic amnesia for a four year period of her life history after a severe stressful event. We performed the fMRI study for a face recognition task using stimulation with three kinds of face photographs: recognizable familiar faces, unrecognizable friends' faces due to the psychogenic amnesia, and unfamiliar control faces. Different activation patterns between the recognizable faces and unrecognizable faces were found in the limbic area, and especially in the amygdala and hippocampus

An investigation into Reynolds scaling and solidity for a HATT tidal turbine

Scale model testing has formed a vital part of modelling research activities, allowing modelling researchers to validate code and model set ups against experimental data. Generally, scale testing to-date has proceeded at the 1/30th to 1/20th scale which is in line with the size of facilities available for testing such devices. This paper presents a fundamental study into the effects of Reynolds Number and Rotor Solidity when testing HATTs at 1/5th scale, 1/20th scale and 1/30th scale. The paper utilises a mixture of 1/30th scale (0.5 m diameter) experimental data for two, three and four rotor setups, 1/20th scale (0.9m diameters) experimental data for a three-blade rotor setup

IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis

IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)(2) subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)(2) on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)(2) model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)(2) inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor gamma t and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)(2) suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling.1156Ysciescopu