The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx.
Tanshinones and phenolic acids are crucial bioactive compounds biosynthesized in Salvia miltiorrhiza. Methyl jasmonate (MeJA) is an effective elicitor to enhance the production of phenolic acids and tanshinones simultaneously, while yeast extract (YE) is used as a biotic elicitor that only induce tanshinones accumulation. However, little was known about the different molecular mechanism. To identify the downstream and regulatory genes involved in tanshinone and phenolic acid biosynthesis, we conducted comprehensive transcriptome profiling of S. miltiorrhiza hairy roots treated with either MeJA or YE. Total 55588 unigenes were assembled from about 1.72 billion clean reads, of which 42458 unigenes (76.4%) were successfully annotated. The expression patterns of 19 selected genes in the significantly upregulated unigenes were verified by quantitative real-time PCR. The candidate downstream genes and other cytochrome P450s involved in the late steps of tanshinone and phenolic acid biosynthesis pathways were screened from the RNA-seq dataset based on co-expression pattern analysis with specific biosynthetic genes. Additionally, 375 transcription factors were identified to exhibit a significant up-regulated expression pattern in response to induction. This study can provide us a valuable gene resource for elucidating the molecular mechanism of tanshinones and phenolic acids biosynthesis in hairy roots of S. miltiorrhiza.
To better understand the effect of wave-breaking-induced turbulence on the bed, we report a 3-D large-eddy simulation (LES) study of a breaking solitary wave in spilling condition. Using a turbulenceresolving approach, we study the generation and the fate of wave-breaking-induced turbulent coherent structures, commonly known as obliquely descending eddies (ODEs). Specifically, we focus on how these eddies may impinge onto bed. The numerical model is implemented using an open-source CFD library of solvers, called OpenFOAM, where the incompressible 3-D filtered Navier-Stokes equations for the water and the air phases are solved with a finite volume scheme. The evolution of the water-air interfaces is approximated with a volume of fluid method. Using the dynamic Smagorinsky closure, the numerical model has been validated with wave flume experiments of solitary wave breaking over a 1/50 sloping beach. Simulation results show that during the initial overturning of the breaking wave, 2-D horizontal rollers are generated, accelerated, and further evolve into a couple of 3-D hairpin vortices. Some of these vortices are sufficiently intense to impinge onto the bed. These hairpin vortices possess counter-rotating and downburst features, which are key characteristics of ODEs observed by earlier laboratory studies using Particle Image Velocimetry. Model results also suggest that those ODEs that impinge onto bed can induce strong near-bed turbulence and bottom stress. The intensity and locations of these near-bed turbulent events could not be parameterized by near-surface (or depth integrated) turbulence unless in very shallow depth.
To understand the interaction between wave‐breaking induced turbulent coherent structures and suspended sediment transport, we report a Large‐Eddy Simulation (LES) study of wave‐breaking processes over a near‐prototype scale barred beach. The numerical model is implemented using the open‐source CFD toolbox, OpenFOAM®, in which the incompressible three‐dimensional filtered Navier‐Stokes equations for the water and air phases are solved with a finite volume scheme. A volume of fluid (VOF) method is used to capture the evolution of the water‐air interface. The numerical model is validated with measured free surface elevation, turbulence‐averaged flow velocity, turbulent intensity, and for the first time, the intermittency of breaking wave turbulence. Simulation results confirm that as the obliquely descending eddies (ODEs) approach the bottom, significant bottom shear stress is generated. Remarkably, the collapse of ODEs onto the bed can also cause drastic spatial and temporal changes of dynamic pressure on the bottom. By allowing sediment to be suspended from the bar crest, intermittently high sediment suspension events and their correlation with high turbulence and/or high bottom shear stress events are investigated. The simulated intermittency of sediment suspension is similar to previous field and large wave flume observations. Coherent suspension events account for only 10% of the record but account for about 50% of the sediment load. Model results suggest that about 60%∼70% of coherent bottom stress events are associated with surface‐generated turbulence. Nearly all the coherent sand suspension events are associated with coherent turbulence events due to wave‐breaking turbulence approaching the bed.
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