Amyloid- peptide (A)-induced death in cerebral endothelial cells (CECs)is preceded by mitochondrial dysfunction and signaling events characteristic of apoptosis. Mitochondria-dependent apoptosis engages Bcl-2 family proteins, especially the BH3-only homologues, which play a key role in initiating the apoptotic cascade. Here, we report that the expression of bim, but not other BH3-only members, was selectively increased in cerebral microvessels isolated from 18-month-old APPsw (Tg2576) mice, a model of cerebral amyloid angiopathy (CAA), suggesting a pivotal role for Bim in A-induced cerebrovascular degeneration in vivo. A similar expression profile was observed in A-treated CECs. Furthermore, A induction of bim expression involved a pro-apoptotic transcription factor, FKHRL1. FKHRL1 bound to a consensus sequence in the bim promoter region and was activated by A before bim expression. FKHRL1 activity was negatively regulated by phosphorylation catalyzed by Akt, an anti-apoptotic kinase. Akt upregulation by adenoviral gene transfer inhibited A-induced FKHRL1 activation and bim induction. In addition, A increased the activity of protein phosphatase 2A (PP2A), a ceramide-activated protein phosphatase. Suppression of PP2A activity by RNA interference or a specific inhibitor, okadaic acid, effectively suppressed A-induced Akt inactivation and FKHRL1 activation, leading to an attenuation of bim expression and cell death in CECs. Coimmunoprecipitation experiments revealed that A enhanced the binding of the PP2A regulatory subunit PP2AC␣ to Akt. These results implicate PP2A as an early regulator of A-induced bim expression and CEC apoptosis via the Akt/FKHRL1 signaling pathway. We raise the possibility that this pathway may play a role in cerebrovascular degeneration in CAA.
A microgrid (MG) can operate in both grid-tied and autonomous mode. Without the support from the public utility, the control of an autonomous MG is more complex due to its poor system inertia. Though energy storage system (ESS) can act as a main power source to maintain system frequency and voltage stability, traditional droop control is usually invalid in practice due to the resistive line of low/medium voltage MG. Virtual impedance control can be a solution to decouple the active and reactive power allocations among ESSs. However, the control bandwidth is reduced since it requires low-pass filters with reduced bandwidth to calculate the average active and reactive power. In this paper, a novel ESSs control method is proposed with V/f droop control (VFDC) and P/Q droop control (PQDC) combined. It can distribute the active and reactive power precisely since the interference of line parameters uncertainty is prevented and system stability is enhanced. The comparison between traditional droop and the hybrid VFDC/PQDC is analyzed based on equivalent circuits. A hybrid VFDC/PQDC-based MG control scheme is proposed and its small-signal stability is analyzed. The proposed method is verified through experimental test on a MG platform with two 100 kVA ESS prototypes.Index Terms-Energy storage system (ESS), microgrid (MG), P/Q droop, small-signal model, V/f droop.
Membranous nephropathy (MN, also known as membranous glomerulopathy) is one of the many glomerular diseases causing nephrotic syndrome. The literature indicates that autophagy is associated with the homeostasis of podocytes in glomeruli. Curcumin, the main active component in turmeric, has drawn attention for its effective bioactivities against chronic kidney disease. The current study was aimed at assessing the effects of curcumin and exploring the underlying mechanism that mediates autophagy in an animal model of passive Heymann nephritis (PHN) in rats. Passive Heymann nephritis (PHN) was induced in male SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were divided into 3 groups: control ( n = 10 , normal diet), model group ( n = 10 , 0.5% sodium carboxymethylcellulose), and curcumin ( n = 10 , 300 mg/kg/d). The kidney function and oxidative stress indicators were measured using commercial diagnostic kits, and the histomorphology of renal tissues was observed. The number of podocytes was measured by immunohistochemistry. Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the immunofluorescence assay pointing to p62, an autophagic marker. Western blot analyzed the levels of apoptosis, autophagy, PI3K/AKT/mTOR, and Nrf2/HO-1 pathway-associated proteins. The total cholesterol (TC), triglycerides (TG), creatinine (Scr), blood urea nitrogen (BUN), urine volume, and urine albumin of PHN rats were significantly reduced by the administration of curcumin and attenuated renal histomorphological changes in model rats. Meanwhile, curcumin improved the oxidative stress response by decreasing MDA and increasing SOD, GSH, and CAT levels in the kidney of PHN rats. Furthermore, curcumin significantly ameliorated the podocyte loss, along with the fusion, and increased the autophagic vacuoles compared to the PHN control rats. In addition, curcumin downregulated the expression of Bax, Caspase-3, p62, PI3K, p-AKT, and p-mTOR proteins and upregulated the Bcl-2, beclin1, LC3, Nrf2, and HO-1 levels in this animal model. The results provide a scientific basis that curcumin could significantly alleviate the development of MN by inducing autophagy and alleviating renal oxidative stress through the PI3K/AKT/mTOR and Nrf2/HO-1 pathways.
PTEN/Akt/mTOR signaling stimulated by high concentration of glucose is regulated by Cx43 overexpression, which unveils part of the molecular mechanism of Cx43 in regulating hyperglycemia-induced hypertrophy.
We report superluminal propagation in optical fibers using Brillouin lasing oscillation in a ring cavity. Negative group velocity propagation through a 10-m single mode fiber has been experimentally demonstrated. An advancement of 221.2 ns was observed before the input signal, which was achieved with a very high slope efficiency of 211.3 ns/dB. This indicates that this way is suitable for long-distance low-loss superluminal propagation via optical fibers. Correspondingly, the group velocity is -0.151c and the group index is -6.636-the highest group velocity ever reported for optical fibers.
Birefringent effect dependent on magnetic intensity and wavelength in a water-based Fe3O4 magnetic fluid over the wavelength range of 400–700nm is studied in this letter. The results are compared with the theory proposed by Llewellyn [J. Phys. D 16, 95 (1983)], in which the optical anistropic properties of the magnetic fluid due to the aggregation of the particles at a relatively low density is suggested. It is shown that the degree of aggregation corresponds to the value of the axial ratio of the aggregated particles. So does the magnitude of the birefringence.
Drought is a major agricultural menace reducing crop productivity and limiting the successful realization of land potential throughout the world. Therefore, breeding common wheat with improved drought-tolerance via genetic manipulation is of great importance. We have introduced the betA gene encoding choline dehydrogenase from Escherichia coli into common wheat (Triticum aestivum L.) by Agrobacterium-mediated transformation. Various levels of expression of the betA gene were confirmed by RT-PCR among the transgenic lines and different levels of glycine betaine accumulation were detected in these lines. Several wheat transgenic lines with different betA expression levels in the T3 generation and wild-type (WT) were selected to test their performance under drought stress conditions. Water deficit in plants caused a reduction in photosynthesis and activity of the PSII complex and resulted in increased accumulation of osmolytes. Drought stress also led to lower membrane stability along with much higher activities of superoxide dismutase and peroxidase in all wheat lines. However, wheat lines that were transgenic for the betA gene were less injured and exhibited greater root length and growth compared with the WT. It was concluded that the amount of injury to the wheat plants was negatively correlated with the level of accumulation of glycine betaine, and the glycine betaine acted as an important osmoprotectant in transgenic plants to improve root growth, and enhance the resistance of transgenic plants to drought stress.
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