Group V Phospholipase A2 Induces Leukotriene Biosynthesis in Human Neutrophils through the Activation of Group IVA Phospholipase A2

We reported previously that exogenously added human group V phospholipase A2 (hVPLA2) could elicit leukotriene B4 (LTB4) biosynthesis in human neutrophils (Han, S. K., Kim, K. P., Koduri, R., Bittova, L., Munoz, N. M., Leff, A. R., Wilton, D. C., Gelb, M. H., and Cho, W. (1999) J. Biol. Chem. 274, 11881-11888). To determine the mechanism of the hVPLA2-induced LTB4 biosynthesis in neutrophils, we thoroughly examined the effects of hVPLA2 and their lipid products on the activity of group IVA cytosolic PLA2 (cPLA2) and LTB4 biosynthesis under different conditions. As low as 1 nM exogenous hVPLA2 was able to induce the release of arachidonic acid (AA) and LTB4. Typically, AA and LTB4 were released in two phases, which were synchronized with a rise in intracellular calcium concentration ([Ca2+]i) near the perinuclear region and cPLA2 phosphorylation. A cellular PLA2 assay showed that hVPLA2 acted primarily on the outer plasma membrane, liberating fatty acids and lysophosphatidylcholine (lyso-PC), whereas cPLA2 acted on the perinuclear membrane. Lyso-PC and polyunsaturated fatty acids including AA activated cPLA2 and 5-lipoxygenase by increasing [Ca2+]i and inducing cPLA2 phosphorylation, which then led to LTB4 biosynthesis. The delayed phase was triggered by the binding of secreted LTB4 to the cell surface LTB4 receptor, which resulted in a rise in [Ca2+]i and cPLA2 phosphorylation through the activation of mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2. These results indicate that a main role of exogenous hVPLA2 in neutrophil activation and LTB4 biosynthesis is to activate cPLA2 and 5-lipoxygenase primarily by liberating from the outer plasma membrane lyso-PC that induces [Ca2+]i increase and cPLA2 phosphorylation and that hVPLA2-induced LTB4 production is augmented by the positive feedback activation of cPLA2 by LTB4

Approximation of most penetrating particle size for fibrous filters considering Cunningham slip correction factor

In the estimation of the aerosol single fiber efficiency using fibrous filters, there is a size range, where the particles penetrate most effectively through the fibrous collectors, and corresponding minimum single fiber efficiency. For small particles in which the diffusion mechanism is dominant, the Cunningham slip correction factor (Cc) affects the single fiber efficiency and the most penetrating particle size (MPPS). Therefore, for accurate estimation, Cc is essential to be considered. However, many previous studies have neglected this factor because of its complexity and the associated difficulty in deriving the appropriate parameterization particularly for the MPPS. In this study, the expression for the MPPS, and the corresponding expression for the minimum single fiber efficiency are analytically derived, and the effects of Cc are determined. In order to accommodate the slip factor for all particle-size ranges, Cc is simplified and modified. Overall, the obtained analytical expression for the MPPS is in a good agreement with the exact solution

An Electrophilic Deguelin Analogue Inhibits STAT3 Signaling in H-Ras-Transformed Human Mammary Epithelial Cells: The Cysteine 259 Residue as a Potential Target

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signals that are often constitutively activated in many cancerous or transformed cells and some stromal cells in the tumor microenvironment. Persistent STAT3 activation in malignant cells stimulates proliferation, survival, angiogenesis, invasion, and tumor-promoting inflammation. STAT3 undergoes activation through phosphorylation on tyrosine 705, which facilitates its dimerization. Dimeric STAT3 translocates to the nucleus, where it regulates the transcription of genes involved in cell proliferation, survival, etc. In the present study, a synthetic deguelin analogue SH48, discovered by virtual screening, inhibited the phosphorylation, nuclear translocation, and transcriptional activity of STAT3 in H-ras transformed human mammary epithelial MCF-10A cells (MCF10A-ras). We speculated that SH48 bearing an alpha,beta-unsaturated carbonyl group could interact with a thiol residue of STAT3, thereby inactivating this transcription factor. Non-electrophilic analogues of SH48 failed to inhibit STAT3 activation, lending support to the above supposition. By utilizing a biotinylated SH48, we were able to demonstrate the complex formation between SH48 and STAT3. SH48 treatment to MCF10A-ras cells induced autophagy, which was verified by staining with a fluorescent acidotropic probe, LysoTracker Red, as well as upregulating the expression of LC3II and p62. In conclusion, the electrophilic analogue of deguelin interacts with STAT3 and inhibits its activation in MCF10A-ras cells, which may account for its induction of autophagic death.

Analysis Technique on Water Permeability in Concrete with Cold Joint considering Micro Pore Structure and Mineral Admixture

Cold joint in concrete due to delayed concrete placing may cause a reduced shear resistance and increased water permeation. This study presents an analytical model based on the concept of REV (Representative Element Volume) to assess the effect of water permeability in cold joint concrete. Here, OPC (Ordinary Portland Cement) concrete samples with cold joint are prepared and WPT (Water Permeability Test) is performed on the samples cured for 91 days. In order to account for the effect of GGBFS (Granulated Ground Blast Furnace Slag) on water permeability, concrete samples with the same W/B (Water to Binder) ratio and 40% replacement ratio of GGBFS are tested as well. Utilizing the previous models handling porosity and saturation, the analysis technique for equivalent water permeability with effective cold joint width is proposed. Water permeability in cold joint increases to 140.7% in control case but it decreases to 120.7% through GGBFS replacement. Simulation results agree reasonably well with experimental data gathered for sound and cold joint concrete

Assessment of RELAP/MOD3 using BETHSY 6.2TC 6-inch cold leg side break comparative test

This report presents the results of the RELAP5/MOD3 Version 7j assessment on BETHSY 6.2TC. BETHSY 6.2TC test corresponding to a six inch cold leg break LOCA of the Pressurizer Water Reactor(PWR). The primary objective of the test was to provide reference data of two facilities of different scales (BETHSY and LSTF facility). On the other hand, the present calculation aims at analysis of RELAP5/N4OD3 capability on the small break LOCA simulation, The results of calculation have shown that the RELAP5/MOD3 reasonably predicts occurrences as well as trends of the major phenomena such as primary pressure, timing of loop seal clearing, liquid hold up, etc. However, some disagreements also have been found in the predictions of loop seal clearing, collapsed core water level after loop seal clearing, and accumulator injection behaviors. For better understanding of discrepancies in same predictions, several sensitivity calculations have been performed as well. These include the changes of two-phase discharge coefficient at the break junction and some corrections of the interphase drag term. As result, change of a single parameter has not improved the overall predictions and it has been found that the interphase drag model has still large uncertainties

Neuropsychological test-based risk prediction of conversion to dementia in amnestic mild cognitive impairment patients: a personal view

The amnestic form of mild cognitive impairment (aMCI) is understood to be a prodromal state of Alzheimer’s disease dementia. As recent studies and clinical trials have started to focus on the early detection of and intervention for Alzheimer’s disease, aMCI has become an important area of study. Due to the heterogeneous clinical course of aMCI, it is often more challenging for a clinician to predict the prognosis of aMCI patients than of those with Alzheimer’s disease dementia patients. Therefore, the ability to predict the clinical course of an aMCI patient based on the patient’s clinical data is crucial in both clinical and research settings. In the current study, we present our findings on the structural and prognostic differences between aMCI and Alzheimer’s disease dementia according to neuropsychological test results. Additionally, we introduce a neuropsychological test-based risk prediction model of the conversion to dementia