4,803 research outputs found

    Meteorin regulates mesendoderm development by enhancing nodal expression

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    During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu

    Multiport Bidirectional SRM Drives for Solar-Assisted Hybrid Electric Bus Powertrain With Flexible Driving and Self-Charging Functions

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    The hybrid electric bus (HEB) presents an emerging solution to exhaust gas emissions in urban transport. This paper proposes a multiport bidirectional switched reluctance motor (SRM) drive for solar-assisted HEB (SHEB) powertrain, which not only improves the motoring performance, but also achieves flexible charging functions. To extend the driving miles and achieve self-charging ability, photovoltaic (PV) panels are installed on the bus to decrease the reliance on fuelsbatteries and charging stations. A bidirectional front-end circuit with a PV-fed circuit is designed to integrate electrical components into one converter. Six driving and five charging modes are achieved. The dc voltage is boosted by the battery in generator control unit (GCU) driving mode and by the charge capacitor in battery driving mode, where the torque capability is improved. Usually, an extra converter is needed to achieve battery charging. In this paper, the battery can be directly charged by the demagnetization current in GCU or PV driving mode, and can be quickly charged by the PV panels and GCUAC grids at SHEB standstill conditions, by utilizing the traction motor windings and integrated converter circuit, without external charging converters. Experiments on a three-phase 128 SRM confirm the effectiveness of the proposed drive and control scheme

    Carbon Monoxide Protects against Hepatic Ischemia/Reperfusion Injury via ROS-Dependent Akt Signaling and Inhibition of Glycogen Synthase Kinase 3β

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    Carbon monoxide (CO) may exert important roles in physiological and pathophysiological states through the regulation of cellular signaling pathways. CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating intracellular redox status and by inhibiting inflammatory, apoptotic, and proliferative responses. However, the cellular mechanisms underlying the protective effects of CO in organ I/R injury remain incompletely understood. In this study, a murine model of hepatic warm I/R injury was employed to assess the role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways in the protective effects of CO against inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a crucial role in CO-mediated protection. CO treatment increased the phosphorylation of Akt and GSK3-beta (GSK3β) in the liver after I/R injury. Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the protective effect of CO and decreased the level of phospho-GSK3β after I/R injury. These results suggest that CO protects against liver damage by maintaining GSK3β phosphorylation, which may be mediated by the PI3K/Akt signaling pathway. Our study provides additional support for the therapeutic potential of CO in organ injury and identifies GSK3β as a therapeutic target for CO in the amelioration of hepatic injury

    EFFECTS OF LEISURE SPORTS PARTICIPATION PERIOD ON BALANCE AND THE LOWER EXTREMITY ASYMMETRY

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    The aim of this study was to investigate the effect of the sports participation on balance measurements and lower extremity symmetry. Eighty healthy middle-aged adults (male 35, women 45) were participated in this study. COP related variables were selected for both double and single leg standing as center of pressure anterior posterior (COP-AP) and medial lateral (COP-ML) displacement, center of pressure mean velocity (COP-MV), center of pressure area (COP-Area), and the symmetry index (SI) of dominant and non-dominant leg. Only the COP-MV showed statistically difference for both double and single leg standing test. However, no significant differences were observed for single leg standing asymmetries. As a result, long term sports participation has positive effects on balance which can be helpful to prevent falls in middle-aged adults

    A Multi-Port Bidirectional Power Conversion System for Reversible Solid Oxide Fuel Cell Applications

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    Loss of APD1 in Yeast Confers Hydroxyurea Sensitivity Suppressed by Yap1p Transcription Factor

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    Ferredoxins are iron-sulfur proteins that play important roles in electron transport and redox homeostasis. Yeast Apd1p is a novel member of the family of thioredoxin-like ferredoxins. In this study, we characterized the hydroxyurea (HU)-hypersensitive phenotype of apd1Δ cells. HU is an inhibitor of DNA synthesis, a cellular stressor and an anticancer agent. Although the loss of APD1 did not influence cell proliferation or cell cycle progression, it resulted in HU sensitivity. This sensitivity was reverted in the presence of antioxidant N-acetyl-cysteine, implicating a role for intracellular redox. Mutation of the iron-binding motifs in Apd1p abrogated its ability to rescue HU sensitivity in apd1Δ cells. The iron-binding activity of Apd1p was verified by a color assay. By mass spectrometry two irons were found to be incorporated into one Apd1p protein molecule. Surprisingly, ribonucleotide reductase genes were not induced in apd1Δ cells and the HU sensitivity was unaffected when dNTP production was boosted. A suppressor screen was performed and the expression of stress-regulated transcription factor Yap1p was found to effectively rescue the HU sensitivity in apd1Δ cells. Taken together, our work identified Apd1p as a new ferredoxin which serves critical roles in cellular defense against HU.published_or_final_versio

    Targeting EZH2 Regulates Tumor Growth and Apoptosis Through Modulating Mitochondria Dependent Cell-Death Pathway in HNSCC

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    EZH2 is a negative prognostic factor and is overexpressed or activated in most human cancers including head and neck squamous cell carcinoma (HNSCC). Analysis of The Cancer Genome Atlas (TCGA) HNSCC data indicated that EZH2 over-expression was associated with high tumor grade and conferred poor prognosis. EZH2 inhibition triggered cell apoptosis, cell cycle arrest and decreased cell growth in vitro. MICU1 (mitochondrial calcium uptake1) was shown to be down regulated when EZH2 expression was inhibited in HNSCC. When the EZH2 and MICU1 were inhibited, HNSCC cells became susceptible to cell cycle arrest and apoptosis. Mitochondrial membrane potential and cytosolic Ca2+ concentration analysis suggested that EZH2 and MICU1 were required to maintain mitochondrial membrane potential stability. A xenograft tumor model was used to confirm that EZH2 depletion inhibited HNSCC cell growth and induced tumor cell apoptosis. In summary, EZH2 is a potential anti-tumor target in HNSCC
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