Identifying The Function Of The Calpain Small Subunit In The Mechanics Of Cell Migration

Cell migration plays a vital role in many physiological events including: morphogenesis, wound healing, and immune response. Dysfunctional cell migration results in multiple disease states including chronic inflammation, vascular disease, and tumor metastasis, to name a few. Progress in understanding the mechanism of cell migration had been slow until the turn of the century when rapid technological advances in microscopy and omics burst to the forefront. These advances led to the realization that physical factors (dimensions, fluid shear stress, hydrostatic pressure, compression stress, environmental stiffness, and topography) have profound effects on cell migration. This study of cell mechanics has expanded extensively in the past 20 years as with the application of multidisciplinary approaches in nanotechnology, biophysics, and modern cell biology. Given the importance of focal adhesion dynamics in migration and mechanics, we focused on the function of calpain proteases on cell migration. Previously we discovered that when compared to wildtype MEFs, Capn4-/- cells displayed reduced traction force and this was not observed when the large catalytic subunits were silenced respectively or when the endogenous inhibitor calpastatin was overexpressed. In comparison, mechanosensing of localized tension was defunct in cells lacking the large subunits, or calpain 4, or when the holoenzyme activity was inhibited by calpastatin. These results together formed our conclusion that the regulatory small subunit calpain 4 must modulate the production of traction forces independent of the catalytic activity of the calpain holoenzymes, but function together to regulate the mechanosensing of localized tension. In gaining understanding of the mechanics of traction force and mechanosensing of cell migration, we asked how calpain 4 protein regulates traction force. By overexpressing each domain in Capn4-/- cells, we have found that only the overexpression of domain V in Capn4-/- cells rescues the traction force defect, the reduced migration rate, and the abnormal focal adhesion organization. However, only the overexpression of domain VI in Capn4-/- cells restores both the ability to sense mechanical stimuli and the proteolytic activity. These results suggest that domains of calpain 4 function independently in regulating the traction force and sensing the external stimuli. We also asked what other players also function in regulating traction force through calpain 4. We performed a yeast two-hybrid assay and identified basigin to be one of the binding proteins. Further results indicated that inhibition of basigin in MEFs resulted in reduced level of traction force and defective adhesion strength without interfering with the sensing of external stimuli and homeostatic tension of the substrate. Together these results further elucidate the mechanism of cell migration and interplay of traction force and mechanosensing, and establish calpain 4 to be a critical player in the regulation of traction force. Further investigation into this signaling pathway will greatly expand our scope of the mechanical aspects of cell migration and further benefit cell migration related diseases studies

MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.

Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet-induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases

Reproductive Toxicity Assessment of Surface Water of the Tai Section of the Yangtze River, China by in vitro Bioassays Coupled With: Chemical Analysis. Environ. Pollut

a b s t r a c t Reproductive toxicity of organic extracts of the surface water from the Tai section of the Yangtze River was assessed by in vitro cytotoxity assays and selected persistent organic pollutants including PCBs, OCPs and PAHs were quantified by instrumental analysis. Eleven of the US EPA priority PAHs were detected. Individual PAHs were found to range from 0.7 to 20 ng/L. Concentrations of BaP did not exceed the national drinking water source quality standard of China. However, a 286-fold concentrated organic extract induced significant reproductive toxicity in adult male rats. The morphology of cells, MTT assay and LDH release assay were all affected by exposure to the organic extracts of water. The results of the reproductive toxicity indicated that PAHs posed the greatest risk of the chemicals studied. The compounds present in the water could be bioconcentrated and result in adverse effects

Parametric Transient Stability Constrained Optimal Power Flow Solved by Polynomial Approximation Based on the Stochastic Collocation Method

To better respond to the impact of power system-uncertain parameters on transient stability, a novel model named the parametric transient stability constrained optimal power flow (parametric TSCOPF) is proposed. It seeks the optimal control scheme of transient stability constrained optimal power flow (TSCOPF) expressed by the function of uncertain parameters in power systems. The key difficulty to solve this model lies in that the relationship between the parametric TSCOPF solution and uncertain parameters is implicit, which is hard to derive generally. To this end, this paper approximates the optimal solution of parametric TSCOPF by polynomial expressions of uncertain parameters based on the stochastic collocation method. First, the parametric TSCOPF model includes both uncertain parameters and transient stability constraints, in which the transient stability constraint is constructed as a set of polynomial expressions using the SCM. Then, to derive the relationship between the parametric TSCOPF solution and uncertain parameters, the SCM is applied to the parametric Karush–Kuhn–Tucker (KKT) conditions of the parametric TSCOPF model, so that the optimal solution of the parametric TSCOPF is approximated by using polynomial expressions with respect to uncertain parameters. The proposed parametric TSCOPF model has been tested on a 3-machine, 9-bus system, and the IEEE 145-bus system, which verifies the effectiveness of the proposed method

Research on Distribution Network Side Shared Energy Storage Business Model under Double Carbon Strategy

Under the goal of the national dual carbon strategy, favorable policies related to national and local energy storage appear frequently, and the era of large-scale energy storage comes. Based on the analysis of relevant national energy storage policies, this paper points out that under the single business model of energy storage, its energy storage resources will lead to a large number of idle waste and low economic benefits, and then leads to the necessity of shared energy storage business model, Compared with the traditional single energy storage business model, shared energy storage has wider sources of income and higher return on investment; This paper expounds the characteristics of the multi-agent shared energy storage business model participated by the third party, points out the interest relationship among its subjects, and then analyzes the typical application scenarios and business model of shared energy storage combined with the case of Shandong shared energy storage; Finally, it combs the application technology of shared energy storage, analyzes the bilateral and unilateral transaction interest relationship of shared energy storage, puts forward the transaction mode of standardizing its single and bilateral cost sharing, and then studies the transaction architecture of shared energy storage system for multi-agent users in distribution network

Electrocatalytic Degradation of Phenolic Wastewater Using a Zero-Gap Flow-Through Reactor Coupled with a 3D Ti/RuO₂-TiO₂@Pt Electrode

In this study, the performance of a zero-gap flow-through reactor with three-dimensional (3D) porous Ti/RuO2-TiO2@Pt anodes was systematically investigated for the electrocatalytic oxidation of phenolic wastewater, considering phenol and 4-nitrophenol (4-NP) as the target pollutants. The optimum parameters for the electrochemical oxidation of phenol and 4-NP were examined. For phenol degradation, at an initial concentration of 50 mg/L, initial pH of 7, NaCl concentration of 10.0 g/L, current density of 10 mA/cm2, and retention time of 30 min, the degradation efficiency achieved was 95.05%, with an energy consumption of 15.39 kWh/kg; meanwhile, for 4-NP, the degradation efficiency was 98.42% and energy consumption was 19.21 kWh/kg (at an initial concentration of 40 mg/L, initial pH of 3, NaCl concentration of 10.0 g/L, current density of 10 mA/cm2, and retention time of 30 min). The electrocatalytic oxidation of phenol and 4-NP conformed to the pseudo-first-order kinetics model, and the k values were 0.2562 min−1 and 0.1736 min−1, respectively, which are 1.7 and 3.6-times higher than those of a conventional electrolyzer. Liquid chromatography–mass spectrometry (LC–MS) was used to verify the intermediates formed during the degradation of phenol or 4-NP and a possible degradation pathway was provided. The extremely narrow electrode distance and the flow-through configuration of the zero-gap flow-through reactor were thought to be essential for its lower energy consumption and higher mass transfer efficiency. The zero-gap flow-through reactor with a novel 3D porous Ti/RuO2-TiO2@Pt electrode is a superior alternative for the treatment of industrial wastewater

Research on Distribution Network Side Shared Energy Storage Business Model under Double Carbon Strategy

Under the goal of the national dual carbon strategy, favorable policies related to national and local energy storage appear frequently, and the era of large-scale energy storage comes. Based on the analysis of relevant national energy storage policies, this paper points out that under the single business model of energy storage, its energy storage resources will lead to a large number of idle waste and low economic benefits, and then leads to the necessity of shared energy storage business model, Compared with the traditional single energy storage business model, shared energy storage has wider sources of income and higher return on investment; This paper expounds the characteristics of the multi-agent shared energy storage business model participated by the third party, points out the interest relationship among its subjects, and then analyzes the typical application scenarios and business model of shared energy storage combined with the case of Shandong shared energy storage; Finally, it combs the application technology of shared energy storage, analyzes the bilateral and unilateral transaction interest relationship of shared energy storage, puts forward the transaction mode of standardizing its single and bilateral cost sharing, and then studies the transaction architecture of shared energy storage system for multi-agent users in distribution network

Electric supplementary heating technology of municipal heating for city heat exchange station

Municipal heating in northern areas generally suffers from heat sources, heat grid gaps, and high dependence on fossil fuels. It is difficult to guarantee the heating effect of incremental buildings at the end of the building, and relying on traditional capacity expansion methods has caused a waste of social resources to a certain extent. A “no capacity increase” municipal heating electric supplementary heating technology for urban heat exchange stations is proposed. First, the design concept of the electric supplementary heating system is explained. Then, the investment calculation model of the electric supplementary heating system is established. Finally, an office building in Shijingshan, Beijing is used as a research example to perform simulation calculations