TGF-β1-Induced Expression of the Poor Prognosis SERPINE1/PAI-1 Gene Requires EGFR Signaling: A New Target for Anti-EGFR Therapy

Increased transforming growth factor-β (TGF-β) expression and epidermal growth factor receptor (EGFR) amplification accompany the emergence of highly aggressive human carcinomas. Cooperative signaling between these two growth factor/receptor systems promotes cell migration and synthesis of stromal remodeling factors (i.e., proteases, protease inhibitors) that, in turn, regulate tumor invasion, neo-angiogenesis and inflammation. ranscript profiling of transformed human cells revealed that genes encoding wound healing, matrix remodeling and cell cycle proteins (i.e., the “tissue repair” transcriptome) are significantly up-regulated early after growth factor stimulation. The major inhibitor of plasmin generation, plasminogen activator inhibitor-1 (PAI-1), is among the most highly induced transcripts during the phenotypic transition initiated by TGF-β maximal expression requires EGFR signaling. PAI-1 induction occurs early in the progression of incipient epidermal squamous cell carcinoma (SCC) and is a significant indicator of poor prognosis in epithelial malignancies. Mouse modeling and molecular genetic analysis of complex systems indicates that PAI-1 regulates the temporal/spatial control of pericellular proteolysis, promotes epithelial plasticity, inhibits capillary regression and facilitates stromal invasion. Defining TGF-β1-initiated signaling events that cooperate with an activated EGFR to impact the protease-protease inhibitor balance in the tumor microenvironment is critical to the development of novel therapies for the clinical management of human cancers

Potentiality of benthic dinoflagellate cultures and screening of their bioactivities in Jeju Island, Korea

Eleven strains of benthic dinoflagellates (Amphidinium carterae (D1), Prorocentrum rhathymum (D2),Symbiodinium sp. (D3), Coolia malayensis 1 (D4), Ostreopsis ovata 1 (D5), Ostreopsis ovata 2 (D6),Coolia malayensis 2 (D7), Amphidinium operculatum 1 (D8), Heterocapsa psammophila (D9), Cooliamalayensis 3 (D10) and Amphidinium operculatum 2 (D11)) were collected in Jeju Island, Korea and cultured in 20 L carboys after establishing unialgal cultures. Their growth potential and biomass productivity were evaluated using two different culture media (IMK and f/2 medium); it was found thatIMK medium has the potential to culture benthic dinoflagellates compared to commonly used f/2 medium. Among the benthic dinoflagellates, A. carterae (D1) had the maximum cell density (148.6 × 103 cells mL-1), growth rate (0.317 ± 0.01 divisions day-1) and biomass (0.260 ± 0.03 g L-1 dry weight) in IMK medium at 20 days of culture. Also, screened bioactivities among the methanolic extracts of cultured dinoflagellates showed A. carterae (D1) to have the highest antioxidant and  anti-inflammatory effect and O. ovata 1 (D5) had the highest anticancer activity compared to the other strains. Taken together, this is the first report on the growth potential and biomass production of benthic dinoflagellate strains isolated from Jeju Island in appropriate culture medium as well as their importance in potential pharmacological applications.Key words: Amphidinium carterae, benthic dinoflagellates, biomass, bioactivities, culture conditions, Jeju Island

Effect of physical tree characterisitcs and substrate Condition on maximum overturning moment

Effects of physical tree characteristics and soil shear strength on overturning moment due to flooding were investigated using Salix babylonica and Juglans ailanthifolia, exotic and invasive plants in Japanese rivers. Tree pulling experiments were conducted, and the resulting damage was examined in order to assess the effects of physical tree characteristics on the maximum overturning moment (Mmax). In situ soil shear strength tests were conducted in order to measure soil strength parameters. The effects of species differences on the Mmax were examined by analysis of the root architecture. S. babylonica has a heart-root system that produces a greater overturning moment due to the strong root anchorage and the large amount of substrate that must be mobilized during overturning. J. ailanthifolia has a plate-root system that produces a smaller overturning moment. However, trees with the plate-root system may withstand overturning better due to an increased root:shoot ratio. Considering the strategy of J. ailanthifolia to increase the root:shoot ratio for anchoring in the substrate, the trunk volume index (height*Dbh 2) is a better parameter than Dbh 2 because it indirectly involves the difference in belowground volume and surface area. Different soil cohesion values were found at different experimental sites, and the average Mmax for overturning each species decreased linearly with increasing soil cohesion

Engineering properties and microstructure of a sustainable roof tile manufactured with waste rice husk ash and ceramic sludge addition

Clay replacement with waste rice husk ash (RHA) and ceramic sludge (CS), helps to reduce the consumption of natural clay and solves the ecological issues created by waste disposal. In this study, properties of waste RHA and CS added fired clay tile were investigated, focusing on structural, durability, thermal performance as well as the water quality of the harvested run-off from fired clay roof tiles manufactured in an industrial scale plant. Tiles were cast by clay replacement with waste RHA and CS in four mixtures: 10 %RHA and 0 % CS, 10 % RHA and 10 % CS, 10 % RHA and 15 % CS, and 10 % RHA and 20 % CS (by weight). For 10 %RHA and 10 %CS tiles, dry mass was reduced by 4.9 %, compared with conventional roof tiles, promising a light weight roof tile. Roof tiles with 10 % RHA and 10 %CS showed a transverse breaking load of 1519 N, whereas that of 20 %CS tiles showed 1427 N, indicating that a further 6.5 % strength improvement can be achieved with clay replacement with a combination of two waste materials. Clay replacement with 10 % RHA and 10 % CS resulted in water absorption of 15.25 %. When increasing the clay replacement with combined waste from 10% (10 %RHA and 0%CS) to 30 % (10%RHA and 20 %CS), weight gain due to acid and alkaline attacks reduced from 3.5% to 3.0%, and from 2.2 % to 1.6 %, respectively, indicating enhanced durability performance by incorporating combined waste. High porosity, also confirmed by SEM, contributed to enhanced thermal performance: tile with 10 % RHA and 10 % CS achieved 4.4 °C temperature reduction, compared to the conventional tile. pH value and total solid concentration of run-off water were in the range of recommended values of water for agricultural purposes, ensuring that the collected run-off can be utilized as an alternative water source for potable activities.publishedVersio

Redox-Induced Src Kinase and Caveolin-1 Signaling in TGF-β1-Initiated SMAD2/3 Activation and PAI-1 Expression

Plasminogen activator inhibitor-1 (PAI-1), a major regulator of the plasmin-based pericellular proteolytic cascade, is significantly increased in human arterial plaques contributing to vessel fibrosis, arteriosclerosis and thrombosis, particularly in the context of elevated tissue TGF-β1. Identification of molecular events underlying to PAI-1 induction in response to TGF-β1 may yield novel targets for the therapy of cardiovascular disease.Reactive oxygen species are generated within 5 minutes after addition of TGF-β1 to quiescent vascular smooth muscle cells (VSMCs) resulting in pp60(c-src) activation and PAI-1 expression. TGF-β1-stimulated Src kinase signaling sustained the duration (but not the initiation) of SMAD3 phosphorylation in VSMC by reducing the levels of PPM1A, a recently identified C-terminal SMAD2/3 phosphatase, thereby maintaining SMAD2/3 in an active state with retention of PAI-1 transcription. The markedly increased PPM1A levels in triple Src kinase (c-Src, Yes, Fyn)-null fibroblasts are consistent with reductions in both SMAD3 phosphorylation and PAI-1 expression in response to TGF-β1 compared to wild-type cells. Activation of the Rho-ROCK pathway was mediated by Src kinases and required for PAI-1 induction in TGF-β1-stimulated VSMCs. Inhibition of Rho-ROCK signaling blocked the TGF-β1-mediated decrease in nuclear PPM1A content and effectively attenuated PAI-1 expression. TGF-β1-induced PAI-1 expression was undetectable in caveolin-1-null cells, correlating with the reduced Rho-GTP loading and SMAD2/3 phosphorylation evident in TGF-β1-treated caveolin-1-deficient cells relative to their wild-type counterparts. Src kinases, moreover, were critical upstream effectors of caveolin-1(Y14) phosphoryation and initiation of downstream signaling.TGF-β1-initiated Src-dependent caveolin-1(Y14) phosphorylation is a critical event in Rho-ROCK-mediated suppression of nuclear PPM1A levels maintaining, thereby, SMAD2/3-dependent transcription of the PAI-1 gene

Environmental Preferences of Yellowfin Tuna in the North East Indian Ocean: An Application of Satellite Data to Longline Catches

Abstract: Development of state-of-the-art methodologies to minimise search time and to increase the fishing efficiency of high seas fishery are vital for fishing success. It, minimise the operational cost as well as fishing duration that save the fish quality. Understanding of the ocean environment and their preferences of Yellowfin Tuna (YFT) are important aspect to addresses the fishing uncertainty thereby ensuring the expected catch during a short period of time. Environmental parameters such as temperature, chlorophyll and dynamic height of the sea surface were obtained from remote sensing satellites and a YFT catch dataset was obtained from Sri Lankan longliners. The results of the data analyses have shown that the relationships between oceanographic parameters and YFT catch rates were found significant. These relations are capable of predicting fishable aggregations of YFT using near-real time satellite observations. High frequencies of YFT catches were found in the areas where Sea Surface Temperature (SST) varied primarily between 28-30C. The corresponding Sea Surface Heights (SSH) ranged from 205-215 cm and Sea Surface Clorophyll_a (SSC) concentration ranged from 0.1-0.4 mg/m 3 . The relationships between catch rates and the three environmental variables have been tested with the Empirical Cumulative Distribution Function (ECDF). The degrees of differences between the ECDF and catch-weighted cumulative distributions of the three variables are statistically significant (p<0.01). The strongest association showed between catch rates and SSC while SSH showed the lowest. The results obtained from a Generalized Additive Model (GAM) have shown that the space-time factor is well above the ocean environmental factors and the oceanographic factors are also in significant levels (p<0.05). Therefore, the migratory pathway is an essential factor in predicting YFT inhabitants in the northeast Indian Ocean