Gadd45a promotes DNA demethylation through TDG

Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)—initiated oxidative demethylation. The connection of Gadd45a with oxidative demethylation is evidenced by the enhanced activation of a methylated reporter gene in HEK293T cells expressing Gadd45a in combination with catalytically active TDG and Tet. Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci most of which are also targets of TDG and show 5fC enrichment in TDG-deficient cells. These observations indicate that the demethylation effect of Gadd45a is mediated by TDG activity. This finding thus unites Gadd45a with the recently defined Tet-initiated demethylation pathwa

Multiple Roles for the Non-Coding RNA SRA in Regulation of Adipogenesis and Insulin Sensitivity

Peroxisome proliferator-activated receptor-γ (PPARγ) is a master transcriptional regulator of adipogenesis. Hence, the identification of PPARγ coactivators should help reveal mechanisms controlling gene expression in adipose tissue development and physiology. We show that the non-coding RNA, Steroid receptor RNA Activator (SRA), associates with PPARγ and coactivates PPARγ-dependent reporter gene expression. Overexpression of SRA in ST2 mesenchymal precursor cells promotes their differentiation into adipocytes. Conversely, knockdown of endogenous SRA inhibits 3T3-L1 preadipocyte differentiation. Microarray analysis reveals hundreds of SRA-responsive genes in adipocytes, including genes involved in the cell cycle, and insulin and TNFα signaling pathways. Some functions of SRA may involve mechanisms other than coactivation of PPARγ. SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. SRA promotes S-phase entry during mitotic clonal expansion, decreases expression of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, and increases phosphorylation of Cdk1/Cdc2. SRA also inhibits the expression of adipocyte-related inflammatory genes and TNFα-induced phosphorylation of c-Jun NH2-terminal kinase. In conclusion, SRA enhances adipogenesis and adipocyte function through multiple pathways

SRA Regulates Adipogenesis by Modulating p38/JNK Phosphorylation and Stimulating Insulin Receptor Gene Expression and Downstream Signaling

The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did or did not overexpress SRA into adipocytes using combinations of methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA overexpression promotes full adipogenesis in part by stimulation of insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells. Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor (IR) mRNA and protein levels, which led to decreased autophosphorylation of IRβ and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. This likely reflects a stimulatory role of SRA on IR transcription, as transfection studies showed that SRA increased expression of an IR promoter-luciferase reporter construct

Cosmic Artifacts: Wanderer's Lament

http://deepblue.lib.umich.edu/bitstream/2027.42/111696/1/ruichuan_1429860675.pd

Effect of Carbon Target Current on Ultralow Frictional Behavior of CrCN Coatings under Glycerol Lubrication

The aim of this paper is to find an effective way to reduce the friction and wear of steel. CrCN coating was deposited on AISI 304 stainless steel by magnetron sputtering technology, and the friction and wear properties of the coating under glycerol lubrication were studied. The hardness of CrCN coatings on stainless steel surface can reach to 17.87 GPa when the carbon target deposition current is 2A. The CrCN coating presents low friction coefficient (COF) under the lubrication of glycerol, a highly efficient green lubricant. When the load is 0.5 N, the lowest friction coefficient is only 0.01. XPS analysis on the wear track suggested that glycerol decomposed during sliding and a fluid lubricating layer was formed, which provides ultralow friction. The paper shows that the glycerol could be used as an efficient lubricant for the CrCN coating

Review of Recent Advances in the Drive Method of Hydraulic Control Valve

Hydraulic control valves are widely used in industrial production, agricultural equipment, construction machinery, and other large power equipment for controlling the pressure and flow of fluids in hydraulic systems. The driving method has a significant impact on the response and control accuracy of hydraulic valves. This paper reviews the driving methods of spools from five aspects: solenoid drive, material expansion drive, motor drive, hydraulic valve drive, and another drive. It summarizes the various schemes currently available for spool drive and analyzes each of them. After optimizing the driving method of the valve core, the control accuracy can reach 3%, and the minimum response time is 7 ms. According to the characteristics of the different drive methods, the differences between them are compared, the advantages and disadvantages of each drive method are analyzed, and the application scenarios for each drive method are identified. Solutions to the drawbacks of the existing drive methods are proposed, which provide directions for further optimization. We have found that solenoid drives are simple to control, low cost, and the most widely used. Material telescopic drives, motor drives, hydraulic valve drives, and other drives are costly, complex to control, and optional for use in special requirement situations. Based on the existing spool drive methods, an outlook on future drive methods is presented. This review facilitates a comprehensive understanding of the drive methods of hydraulic valve spools, points out the shortcomings of the existing drive methods, and is of great significance in improving the existing drive methods and proposing new drive methods. This paper has a positive effect on improving the control accuracy and responsiveness of hydraulic valves

Effect of the Coil Excitation Method on the Performance of a Dual-Coil Inductive Displacement Transducer

A dual-coil inductive displacement transducer is a non-contact type measuring element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural equipment. However, the effect of the coil excitation method on the performance of dual-coil inductive displacement sensors has not been studied. This paper investigates the impact of different coil excitation methods on the operating performance of displacement transducers. The working principle, electromagnetic characteristics, and electrical characteristics were analyzed by building a mathematical model. A transducer measurement device was used to determine the relationship between core displacement and coil inductance. Three coil excitation methods were proposed, and the effects of the three coil excitation methods on the amplitude variation, phase shift, linearity, and sensitivity of the output signal were studied by simulation based on the AD630 chip as the core of the conditioning circuit. Finally, the study’s feasibility was demonstrated by comparing the experiment to the simulation. The results show that, under the uniform magnetic field strength distribution in the coil, the coil voltage variation is proportional to the inductive core displacement. The amplitude variation is the largest for the dual-coil series three-wire (DCSTW) and is the same for the dual-coil series four-wire (DCSFW) and dual-coil parallel differential (DCPD). DCSFW has an enormous phase shift. DCSTW has the best linearity. The research in this paper provides a theoretical basis for selecting a suitable coil excitation, which is conducive to further improving the operating performance of dual-coil inductive displacement transducers

Effect of Excitation Signal on Double-Coil Inductive Displacement Transducer

A double-coil inductive displacement transducer is a non-contact element for measuring displacement and is widely used in large power equipment systems such as construction machinery and agricultural machinery equipment. The type of coil excitation signal has an impact on the performance of the transducer, but there is little research on this. Therefore, the influence of the coil excitation signal on transducer performance is investigated. The working principle and characteristics of the double-coil inductive displacement transducer are analyzed, and the circuit simulation model of the transducer is established. From the aspects of phase shift, linearity, and sensitivity, the effects of a sine signal, a triangle signal, and a pulse signal on the transducer are compared and analyzed. The results show that the average phase shift, linearity, and sensitivity of the sine signal were 11.53°, 1.61%, and 0.372 V/mm, respectively; the average phase shift, linearity and sensitivity of the triangular signal were 1.38°, 1.56%, and 0.300 V/mm, respectively; and the average phase shift, linearity, and sensitivity of the pulse signal were 0.73°, 1.95%, and 0.621 V/mm, respectively. It can be seen that the phase shift of a triangle signal and a pulse signal is smaller than that of a sine signal, which can result in better signal phase-locked processing. The linearity of the triangle signal is better than the sine signal, and the sensitivity of the pulse signal is better than that of the sine signal

Study on Piezomagnetic Effect of Iron Cobalt Alloy and Force Sensor

Based on the nonlinear piezomagnetic equation, the piezomagnetic effect of prismatic iron-cobalt alloy is analyzed by using the ANSYS finite element simulation platform. The variation of the dynamic piezomagnetic coefficient of the iron-cobalt alloy under different bias magnetic fields and different stress was studied through simulation. Referring to the working condition of the tractor force sensor and according to the principle of magnetic circuit superposition, a piezomagnetic force sensor was designed and manufactured using iron-cobalt alloy. According to the electromagnetic theory and piezomagnetic effect, the three-dimensional model and magnetic circuit mathematical model of the sensor are established, and the system simulation model of the piezomagnetic sensor was established based on the MATLAB/Simulink module. The experimental platform of the magnetostrictive force sensor was built to verify the correctness of the simulation model, and the effects of bias magnetic field and force on the output characteristics are studied. The simulation and experimental results show that the maximum piezomagnetic coefficient was 9.2 T/GPA when the bias magnetic field intensity was 14.74 kA/m. The force measuring range of the sensor is 0–120 kN, and the sensor has high sensitivity within 0–80 kN. The sensor has a simple structure, is suitable for the force measurement and control of an electro-hydraulic lifter under heavy load, and can better adapt to the harsh working environment