Circulating microvesicles as mediators of acute pulmonary vascular inflammation

Acute lung injury (ALI) resulting from remote ‘indirect’ causes is a major problem in sepsis and systemic inflammatory response syndrome (SIRS) but the underlying mechanisms are poorly understood. Circulating microvesicles (MVs) have been implicated as long-range mediators of vascular inflammation and their role as biomarkers in sepsis and SIRS has been widely investigated in clinical studies in recent years. However, the in vivo functional roles of MVs in sepsis and ALI have received less attention. Specifically, the role of in vivo MVs in the development of sepsis/SIRS-induced indirect ALI has not been previously evaluated. We hypothesised that circulating microvesicles (MVs) play a crucial role in propagating inflammation to the lungs, contributing to the development of pulmonary vascular inflammation in indirect ALI. The overall aims of this project were to: 1) evaluate MV uptake by pulmonary vascular cells and the mechanisms involved, 2) characterise the intravascular production of MVs in animal models of sepsis and sterile extrapulmonary organ injury, and 3) identify the contribution of in vivo-derived circulating MVs to the development of indirect ALI. The major findings of this work were that during sub-clinical endotoxaemia in mice, lung-marginated Ly6Chigh monocytes become a major target for circulating MV uptake via a phosphatidylserine receptor mechanism1. In mouse models of sepsis and extrapulmonary organ injury, neutrophil- and monocyte-derived MVs were the predominant MV subtypes being produced during endotoxaemia, while platelet- and endothelial-derived MVs were predominant during kidney ischaemia reperfusion injury. When MVs obtained from plasmas of endotoxaemic mice were adoptively transferred to isolated perfused lungs (IPLs), they induced significant increases in lung oedema. Depletion of intravascular lung monocytes by treatment with clodronate liposomes resulted in the reversal of the oedema, demonstrating the role of monocytes in MV-induced ALI. To investigate the contribution of different circulating MV subtypes, we immunoaffinity isolated myeloid (CD11b+) and platelet (CD41+) MVs from endotoxaemic mouse plasmas and transferred these to the IPL. We found that myeloid-MVs induced significant lung oedema and potent release of soluble mediators, whereas platelet-MVs produced a statistically significant, but much lower level of oedema and negligible release of soluble mediators. In summary, these findings indicate an important role of myeloid-derived MVs, particularly those derived from neutrophils and/or monocytes, and their interaction with lung-marginated monocytes in the pathogenesis of pulmonary vascular inflammation in indirect ALI. Further work to elucidate the specific MV molecular effectors mechanism involved will facilitate an enhanced understanding of ALI pathobiology.Open Acces

A new method for determining small earthquake source parameters using short-period P waves

We developed a new technique of inverting short-period (0.5–2 Hz) P waveforms for determining small earthquake (M <3.5) focal mechanisms and moments, where magnitude ~4 events with known source mechanisms are used to calibrate the "unmodeled" structural effect. The calibration is based on a waveform cluster analysis, where we show that clustered events of different sizes, for example, M ~4 versus M ~2, display similar signals in the short-period (SP, 0.5–2 Hz) frequency band, implying propagational stability. Since both M ~4 and M ~2 events have corner frequencies higher than 2 Hz, they can be treated as point sources, and the "unmodeled" structural effect on the SP P waves can be derived from the magnitude 4 events with known source mechanisms. Similarly, well-determined magnitude 2’s can provide calibration for studying even smaller events at higher frequencies, for example, 2–8 Hz. In particular, we find that the "unmodeled" structural effect on SP P waves is mainly an amplitude discrepancy between data and 1D synthetics. The simple function of "amplitude amplification factor" (AAF) defined as the amplitude ratio between data and synthetics provides useful calibration, in that the AAFs derived from different clustered events appear consistent, hence stable and mechanism independent. We take a grid-search approach to determine source mechanisms by minimizing the misfit error between corrected data and synthetics of SP P waves. The validation tests with calibration events demonstrate the importance and usefulness of the AAF corrections in recovering reliable results. We introduce the method with the 2003 Big Bear sequence. However, it applies equally well to other source regions in southern California, because we have shown that the mechanism independence and stability of the AAFs for source regions of 10 km by 10 km are typical. By definition, the AAFs contain the effects from the station site, the path, and crustal scattering. Although isolating their contributions proves difficult, the mechanism independence and stability of the AAFs suggest that they are mainly controlled by the near-receiver structure. Moreover, the ratios between the AAFs for the vertical and radial components from various events at different locations appear consistent, suggesting that these AAF(v)/AAF(r) ratios might be simple functions of site conditions. In this study, we obtained the focal mechanisms and moments for 92 Big Bear events with M_L down to 2.0. The focal planes correlate well with the seismicity patterns, while containing abundant finer-scale fault complexity. We find a linear relationship between log(M_0) and M_L, that is, log(M_0) = 1.12M_L + 17.29, which explains all the data points spanning three orders of magnitude (2.0 < M_L < 5.5)

A new identity for SL(2,C)-characters of the once punctured torus group

We obtain new variations of the original McShane identity for those SL(2,C)-representations of the once punctured torus group which satisfy the Bowditch conditions, and also for those fixed up to conjugacy by an Anosov mapping class of the torus and satisfying the relative Bowditch conditions.Comment: 9 page

Stabilization Of Thickened-Activated Sludge Through The Anoxic-Aerobic Digestion Process

Aerobic digestion is widely used to treat waste-activated sludge and thickened sludge from wastewater treatment plant due to its shorter retention time and achieving the same efficiency in solids volume reduction compared to anaerobic digestion. However, the supernatant and filtrate from the aerobic digestion system contain high concentration of suspended solids. The nitrogen which had been embedded in sludge is solubilized to form ammonical and nitric nitrogen which in tum transferred to the liquor and cause the increase of nitrogen loading in sewage treatment plant. In this study, anoxic-aerobic digestion is applied to remove both the mixed-liquor volatile suspended solids (ML VSS) and soluble nitrogen simultaneously. The objectives of the study are to investigate and evaluate the removal efficiency of both ML VSS and soluble nitrogen by anoxic-aerobic digestion and compared to the aerobic control digesters, with and without lime control. By applying anoxic-aerobic digestion, a comparable of ML VSS reduction was gained to aerobic digestion. 66.12% and 63.00% of MLVSS destruction was found in both anoxic-aerobic digesters, with and without methanol addition respectively

Hair growth and hair tanning activities of mangosteen pericarp water extract on hair dermal papilla cells

Hair graying represents the most common phenomena of human, and the number of men and women who suffer hair loss is increasing in accordance with changes in lifestyle and nutritional balance. Thus, it is important to develop new therapies to enhance hair growth activity as well as hair tanning. In this study, water extract of mangosteen pericarp was used to investigate its hair growth and tanning activities on hair dermal papilla cells. The mangosteen pericarp extract was found to contain 3.706 mg/ml protein, 0.519 mg/ml polysaccharide, 5.103 gallic acid equivalents mg/g total phenolic content and 1.503 quercetin equivalent mg/g total flavonoid content. Mangosteen pericarp extract showed high IC50 values in both 2,2- diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assays (4.142 mg/ml and 2.373 mg/ml, respectively). This indicated that mangosteen pericarp water extract has low antioxidant activity. The effect of mangosteen pericarp extract on the cellular mitochondrial activity, viability and cytotoxicity of hair dermal papilla cells were measured by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide and Sulforhodamine B assays. It was found that the highest concentration of the extract which did not affect the cell viability was 500 µg/ml. For hair growth promoting activity, the degree of hair dermal papilla cells proliferation increased with increasing concentration of extract. By treated the cells with 500 µg/ml of extract, cell proliferation significantly increased by 157.56%, compared to untreated control cells. The mangosteen pericarp extract was found to stimulate melanin synthesis and tyrosinase activity of dermal papilla cells in concentration-dependent manner, up to the highest concentration of 500 µg/ml. The melanin synthesis was more than four-fold as compared to the untreated control group, indicating that this extract could be one of the melanogenic-stimulating agents. This study also showed that mangosteen pericarp extract was more potent and better in comparison with known effective melanogenic agents such as, a-melanocyte stimulating hormone and forskolin in inducing the melanogenic effects of dermal papilla cells. The overall results showed that mangosteen pericarp extract can potentially be used as a safe ingredient for the development of hair growth and hair tanning product