A pivotal role for NF-κB in the macrophage inflammatory response to the myeloperoxidase oxidant hypothiocyanous acid

© 2018 Elsevier Inc. Atherosclerosis is characterised by the infiltration of macrophages at sites of inflammation within the vessel wall and the release of myeloperoxidase (MPO), which forms hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). HOCl is a damaging oxidant implicated in the development of atherosclerosis. Preferential formation of HOSCN occurs under conditions where thiocyanate ions are elevated, as is the case in smokers. HOSCN reacts selectively with thiols, which can result in more enzyme inactivation and damage than HOCl at susceptible sites, which may contribute to atherosclerosis in smokers. In this study, we show that exposure of macrophages to HOSCN results in a time- and dose-dependent increase in the mRNA expression and release of pro-inflammatory cytokines and chemokines, including monocyte chemotactic protein 1, tumour necrosis factor alpha, and interleukins 6, 8 and 1β. At high oxidant concentrations (>200 μM), a significant loss of cellular thiols and increased cell death is observed. HOSCN-induced cytokine/chemokine expression and cell death were decreased on pharmacological inhibition of nuclear factor kappa B. These data highlight a pathway by which HOSCN could promote inflammation and the development of atherosclerosis, in the presence of supra-physiological levels of the precursor thiocyanate, which are achievable by cigarette smoking

Effect of 15-deoxyspergualin on experimental organ transplantation

DSPG had a definite but relatively feeble immunosuppressive effect in rats undergoing heterotopic heart transplantation and in dogs after renal transplantation. The drug was toxic in both species, although less so in rats. In dogs, synergistic interactions with cyclosporine and steroids were not evident

Cordycepin enhances cisplatin apoptotic effect through caspase/MAPK pathways in human head and neck tumor cells

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Calcium buffering in the heart in health and disease

Changes of intracellular Ca2+ concentration regulate many aspects of cardiac myocyte function. About 99% of the cytoplasmic calcium in cardiac myocytes is bound to buffers, and their properties will therefore have a major influence on Ca2+ signaling. This article considers the fundamental properties and identities of the buffers and how to measure them. It reviews the effects of buffering on the systolic Ca2+ transient and how this may change physiologically, and in heart failure and both atrial and ventricular arrhythmias, as well. It is concluded that the consequences of this strong buffering may be more significant than currently appreciated, and a fuller understanding is needed for proper understanding of cardiac calcium cycling and contractility

Valorization of Napier grass via intermediate pyrolysis: Optimization using response surface methodology and pyrolysis products characterization

This study presents first optimization report on pyrolysis oil derived from Napier grass. Effects of temperature, heating rate and nitrogen flow rate on the intermediate pyrolysis of Napier grass biomass in a vertical fixed-bed tubular reactor were investigated collectively. Response surface methodology with central composite design was used for modelling the process and optimization of the process variables. Individual second order polynomial model was found to be adequate in predicting bio-oil, bio-char and non-condensable gas yield. The optimum bio-oil yield of 50.57 wt% was recorded at 600 �C, 50 �C/min and 5 L/min nitrogen flow. The bio-oil obtained throughout this study was two-phase liquid, organic and aqueous phase. The bio-oil, bio-char and non-condensable gas were characterized using standard analytical techniques. The results revealed that the organic phase consists of hydrocarbons and various benzene derivatives, which can be further processed into fuels and valuable chemicals. The aqueous phase was predominantly water, acids, ketones, aldehydes and some phenolics and other water-soluble organics. The non-condensable gas was made up high hydrogen/carbon monoxide ratio suitable for liquid fuel synthesis via Fischer-Tropsch Synthesis. The bio-char was a porous carbonaceous material with high energy content, which can be applied as a solid fuel, adsorbent or source of biofertilizer. This study demonstrated that Napier grass biomass is a viable feedstock for production of high-value bioenergy precursors

The US stock market leads the Federal funds rate and Treasury bond yields

Using a recently introduced method to quantify the time varying lead-lag dependencies between pairs of economic time series (the thermal optimal path method), we test two fundamental tenets of the theory of fixed income: (i) the stock market variations and the yield changes should be anti-correlated; (ii) the change in central bank rates, as a proxy of the monetary policy of the central bank, should be a predictor of the future stock market direction. Using both monthly and weekly data, we found very similar lead-lag dependence between the S&P500 stock market index and the yields of bonds inside two groups: bond yields of short-term maturities (Federal funds rate (FFR), 3M, 6M, 1Y, 2Y, and 3Y) and bond yields of long-term maturities (5Y, 7Y, 10Y, and 20Y). In all cases, we observe the opposite of (i) and (ii). First, the stock market and yields move in the same direction. Second, the stock market leads the yields, including and especially the FFR. Moreover, we find that the short-term yields in the first group lead the long-term yields in the second group before the financial crisis that started mid-2007 and the inverse relationship holds afterwards. These results suggest that the Federal Reserve is increasingly mindful of the stock market behavior, seen at key to the recovery and health of the economy. Long-term investors seem also to have been more reactive and mindful of the signals provided by the financial stock markets than the Federal Reserve itself after the start of the financial crisis. The lead of the S&P500 stock market index over the bond yields of all maturities is confirmed by the traditional lagged cross-correlation analysis.Comment: 12 pages, 7 figures, 1 tabl

Measuring the H I mass function below the detection threshold

We present a Bayesian stacking technique to directly measure the H I mass function (HIMF) and its evolution with redshift using galaxies formally below the nominal detection threshold. We generate galaxy samples over several sky areas given an assumed HIMF described by a Schechter function and simulate the H I emission lines with different levels of background noise to test the technique. We use MULTINEST to constrain the parameters of the HIMF in a broad redshift bin, demonstrating that the HIMF can be accurately reconstructed, using the simulated spectral cube far below the H I mass limit determined by the 5σ flux-density limit, i.e. down to MH I = 107.5 M over the redshift range 0 <z< 0.55 for this particular simulation, with a noise level similar to that expected for the MIGHTEE survey. We also find that the constraints on the parameters of the Schechter function, φ , M , and α can be reliably fit, becoming tighter as the background noise decreases as expected, although the constraints on the redshift evolution are not significantly affected. All the parameters become better constrained as the survey area increases. In summary, we provide an optimal method for estimating the H I mass at cosmological distances that allows us to constrain the HIMF below the detection threshold in forthcoming H I surveys. This study is a first step towards the measurement of the HIMF at high (z > 0.1) redshifts

Weak up-regulation of serum response factor in gastric ulcers in patients with co-morbidities is associated with increased risk of recurrent bleeding

<p>Abstract</p> <p>Background</p> <p>Serum response factor (SRF) is crucial for gastric ulcer healing process. The study determined if gastric ulcer tissues up-regulate SRF and if such up-regulation correlated with co-morbidities and the risk of recurrent bleeding.</p> <p>Methods</p> <p>Ulcer and non-ulcer tissues were obtained from 142 patients with active gastric ulcers for SRF expression assessed by immunohistochemistry. Based on the degree of SRF expression between these two tissue types, SRF up-regulation was classified as strong, intermediate, and weak patterns. The patients were followed-up to determine if SRF up-regulation correlated to recurrent bleeding.</p> <p>Results</p> <p>Gastric ulcer tissues had higher SRF expression than non-ulcer tissues (<it>p </it>< 0.05). Patients with strong SRF up-regulation had lower rates of stigmata of recent hemorrhage (SRH) on the ulcer base than the others (<it>p </it>< 0.05). Multivariate logistic regression confirmed that co-morbidities and weak SRF up-regulation were two independent factors of recurrent gastric ulcer bleeding (<it>p </it>< 0.05). Combining both factors, there was an 8.29-fold (95% CI, 1.31~52.62; <it>p </it>= 0.03) higher risk of recurrent gastric ulcer bleeding.</p> <p>Conclusions</p> <p>SRF expression is higher in gastric ulcer tissues than in non-ulcer tissues. Weak SRF up-regulation, combined with the presence of co-morbidities, increase the risk of the recurrent gastric ulcer bleeding.</p

Mitochondrial genome nucleotide substitution pattern between domesticated silkmoth, Bombyx mori, and its wild ancestors, Chinese Bombyx mandarina and Japanese Bombyx mandarina

Bombyx mori and Bombyx mandarina are morphologically and physiologically similar. In this study, we compared the nucleotide variations in the complete mitochondrial (mt) genomes between the domesticated silkmoth, B. mori, and its wild ancestors, Chinese B. mandarina (ChBm) and Japanese B. mandarina (JaBm). The sequence divergence and transition mutation ratio between B. mori and ChBm are significantly smaller than those observed between B. mori and JaBm. The preference of transition by DNA strands between B. mori and ChBm is consistent with that between B. mori and JaBm, however, the regional variation in nucleotide substitution rate shows a different feature. These results suggest that the ChBm mt genome is not undergoing the same evolutionary process as JaBm, providing evidence for selection on mtDNA. Moreover, investigation of the nucleotide sequence divergence in the A+T-rich region of Bombyx mt genomes also provides evidence for the assumption that the A+T-rich region might not be the fastest evolving region of the mtDNA of insects

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST