No abstract

Regulation of T cell immunity by C5a has been suggested from recent studies. However, the underlying mechanisms, particularly the involved cells and biochemical basis, are not well defined. In this study, the direct modulation of dendritic cell (DC) activation and its function in T cell stimulation by C5a-C5aR interaction and the involved signaling pathways were investigated. We show that DCs from C5aR−/− mice and normal DCs treated with C5aR antagonist have less-activated phenotype characterized with increased IL-10 and decreased IL-12p70 production in response to LPS stimulation, lowered surface expression of MHC class II, B7.2, and consequently have reduced capacity to stimulate allospecific T cells. Conversely, C5a stimulation up-regulates DC activation and its function in allostimulation. Furthermore, stimulation of C5aR mediates the inhibition of cAMP production and protein kinase A activity and is involved in activation of PI3K/AKT and NF-κB signaling in DCs. These results demonstrate that C5a acts directly on C5aR expressed on DCs resulting in the cell activation and subsequently enhances its capacity for allospecific T cell stimulation. It also suggests that NF-κB signaling induced by down-regulation of cAMP/ protein kinase A pathway and up-regulation of PI3K/AKT pathway following C5a stimulation may contribute to up-regulation of DC function.

Satellite observations of tropospheric NO 2 columns are extensively used to infer trends in anthropogenic emissions of nitrogen oxides (NO x ≡ NO + NO 2 ), but this may be complicated by trends in NO x lifetime. Here we use 2004-2018 observations from the Ozone Monitoring Instrument (OMI) satellite-based instrument (QA4ECV and POMINO v2 retrievals) to examine the seasonality and trends of tropospheric NO 2 columns over central-eastern China, and we interpret the results with the GEOS-Chem chemical transport model. The observations show a factor of 3 increase in NO 2 columns from summer to winter, which we explain in GEOS-Chem as reflecting a longer NO x lifetime in winter than in summer (21 h versus 5.9 h in 2017). The 2005-2018 summer trends of OMI NO 2 closely follow the trends in the Multi-resolution Emission Inventory for China (MEIC), with a rise over the 2005-2011 period and a 25 % decrease since. We find in GEOS-Chem no significant trend of the NO x lifetime in summer, supporting the emission trend reported by the MEIC. The winter trend of OMI NO 2 is steeper than in summer over the entire period, which we attribute to a decrease in NO x lifetime at lower NO x emissions. Half of the NO x sink in winter is from N 2 O 5 hydrolysis, which counterintuitively becomes more efficient as NO x emissions decrease due to less titration of ozone at night. The formation of organic nitrates also becomes an increasing sink of NO x as NO x emissions decrease but emissions of volatile organic compounds (VOCs) do not.Published by Copernicus Publications on behalf of the European Geosciences Union.

BackgroundThe clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions.MethodsFor our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD.ResultsCompared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area.ConclusionsThese findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.