Atherosclerotic cardiovascular disease is the leading cause of death in the world which is resulted from complex interactions among multiple genetic and environmental factors （WHO）. Athero- sclerosis ...is a chronic inflammatory disease characterized by accumulation of lipids in the arterial wall （Gofman and Lindgren, 1950）. Tremendous clinical and experimental efforts have been made to reveal the pathogenesis of the disease. Nevertheless, the mechanism of atherosclerosis is still unclear. A suitable animal model to study metabolic disorders and subsequent atherosclerosis is a necessity. The traditional method by feeding high fat diet to establish animal models of atherosclerosis disease is time- consuming and laborious, and in many circumstances, the pheno- types are not consistent among the individual models.
rhml is a major recessive disease resistance locus for Southern corn leaf blight （SCLB）. To further narrow down its genetic position, F2 population and BCIFI population derived from the cross between ...resistant （H95rhm） and susceptible parents （H95） of maize （Zea mays） were constructed. Using newly developed markers, rhml was initially delimited within an interval of 2.5 Mb, and then finally mapped to a 8.56 kb interval between InDel marker IDP961-503 and simple sequence repeat （SSR） marker A194149--1. Three polymorphic markers IDP961-504, IDP B2-3 and A194149-2 were shown to be co-segregated with the rhml locus. Sequence analysis of the 8.56 kb DNA fragment revealed that it contained only one putative gene with a predicted amino acid sequence identical to lysine histidine transporter 1 （LHT1）. Comparative sequence analysis indicated that the LHT1 in H95rhrn harbors a 354 bp insertion in its third exon as compared with that of susceptible alleles in B73, H95 and Mo17. The 354 bp insertion resulted in a truncation of the predicted protein of candidate resistance allele （LHT1-H95rhm）. Our results strongly suggest LHTI as the candidate gene for rhml against SCLB. The tightly linked molecular markers developed in this study can be directly used for molecular breeding of resistance to Southern corn leaf blight in maize.
There have been many recent advances in wireless communication technologies, particularly in the area of wireless sensor networks, which have undergone rapid development and been successfully applied ...in the consumer electronics market. Therefore, wireless networks (WNs) have been attracting more attention from academic communities and other domains. From an industrial perspective, WNs present many advantages including flexibility, low cost, easy deployment and so on. Therefore, WNs can play a vital role in the Industry 4.0 framework, and can be used for smart factories and intelligent manufacturing systems. In this paper, we present an overview of industrial WNs (IWNs), discuss IWN features and related techniques, and then provide a new architecture based on quality of service and quality of data for IWNs. We also propose some applications for IWNs and IWN standards. Then, we will use a case from our previous achievements to explain how to design an IWN under Industry 4.0. Finally, we highlight some of the design challenges and open issues that still need to be addressed to make IWNs truly ubiquitous for a wide range of applications.
Allostery is the phenomenon in which a ligand binding at one site affects other sites in the same macromolecule. Allostery has important roles in many biological processes. Theoretically, all ...nonfibrous proteins are potentially allosteric. However, few allosteric proteins have been validated, and the identification of novel allosteric sites remains a challenge. The motion of residues and subunits underlies protein function; therefore, we hypothesized that the motions of allosteric and orthosteric sites are correlated. We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM). Most of the known allosteric site motions showed high correlations with corresponding orthosteric site motions, whereas other surface cavities did not. These high correlations were robust when using different structural data for the same protein, such as structures for the apo state and the orthosteric effector-binding state, whereas the contributions of different frequency modes to motion correlations depend on the given protein. The high correlations between allosteric and orthosteric site motions were also observed in oligomeric allosteric proteins. We applied motion correlation analysis to predict potential allosteric sites in the 23 monomer proteins, and some of these predictions were in good agreement with published experimental data. We also performed motion correlation analysis to identify a novel allosteric site in 15-lipoxygenase (an enzyme in the arachidonic acid metabolic network) using recently reported activating compounds. Our analysis correctly identified this novel allosteric site along with two other sites that are currently under experimental investigation. Our study demonstrates that the motions of allosteric sites are highly correlated with the motions of orthosteric sites. Our correlation analysis method provides new tools for predicting potential allosteric sites.
Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese ...individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.
Increasing heavy metal pollution problems have raised word-wide concerns. Cadmium (Cd), being a highly toxic metal, poses potential risks both to ecosystems and human health. Compared with ...conventional technologies, phytoremediation, being cost-efficient, highly stable and environment-friendly, is believed to be a promising green technology for Cd decontamination. However, Cd can be easily taken up by plants and may cause severe phytotoxicity to plants, thus limiting the efficiency of phytoremediation. Various researches are being done to investigate the effects of exogenous substances on the mitigation of Cd toxicity to plants. Calcium (Ca) is an essential plant macronutrient that involved in various plant physiological processes, such as plant growth and development, cell division, cytoplasmic streaming, photosynthesis and intracellular signaling transduction. Due to the chemical similarity between Ca and Cd, Ca may mediate Cd-induced physiological or metabolic changes in plants. Recent studies have shown that Ca could be used as an exogenous substance to protect plants against Cd stress by the alleviation of growth inhibition, regulation of metal uptake and translocation, improvement of photosynthesis, mitigation of oxidative damages and the control of signal transduction in the plants. The effects of Ca on toxic concentrations of Cd in plants are reviewed. This review also provides new insight that plants with enhanced Ca level have improved resistance to Cd stress.
Abstract
CavityPlus is a web server that offers protein cavity detection and various functional analyses. Using protein three-dimensional structural information as the input, CavityPlus applies ...CAVITY to detect potential binding sites on the surface of a given protein structure and rank them based on ligandability and druggability scores. These potential binding sites can be further analysed using three submodules, CavPharmer, CorrSite, and CovCys. CavPharmer uses a receptor-based pharmacophore modelling program, Pocket, to automatically extract pharmacophore features within cavities. CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities. CovCys automatically detects druggable cysteine residues, which is especially useful to identify novel binding sites for designing covalent allosteric ligands. Overall, CavityPlus provides an integrated platform for analysing comprehensive properties of protein binding cavities. Such analyses are useful for many aspects of drug design and discovery, including target selection and identification, virtual screening, de novo drug design, and allosteric and covalent-binding drug design. The CavityPlus web server is freely available at http://repharma.pku.edu.cn/cavityplus or http://www.pkumdl.cn/cavityplus.
We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched ...molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.
One of the biggest hurdles for the development of metabolism-targeted therapies is to identify the responsive tumor subsets. However, the metabolic vulnerabilities for most human cancers remain ...unclear. Establishing the link between metabolic signatures and the oncogenic alterations of receptor tyrosine kinases (RTK), the most well-defined cancer genotypes, may precisely direct metabolic intervention to a broad patient population. By integrating metabolomics and transcriptomics, we herein show that oncogenic RTK activation causes distinct metabolic preference. Specifically, EGFR activation branches glycolysis to the serine synthesis for nucleotide biosynthesis and redox homeostasis, whereas FGFR activation recycles lactate to fuel oxidative phosphorylation for energy generation. Genetic alterations of EGFR and FGFR stratify the responsive tumors to pharmacological inhibitors that target serine synthesis and lactate fluxes, respectively. Together, this study provides the molecular link between cancer genotypes and metabolic dependency, providing basis for patient stratification in metabolism-targeted therapies.
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•The optimal steel converter slag load was determined as 80gkg−1..•High initial H2O2 concentrations caused a sharp increase in soil temperature.•93.7% of atrazine in the soil was ...degraded with a 3-time addition of 10% H2O2.•Steel converter slag catalyzed Fenton-like oxidation slightly increased soil pH.•A considerable amount of dissolved organic carbon released during the treatment.
This is the premier study reporting the remediation of atrazine contaminated soil with steel converter slag (SCS) catalyzed Fenton-like process. The effects of various operating parameters, such as SCS loads and H2O2 concentrations were evaluated with respect to the removal efficiency of atrazine. Results show the optimal SCS load and H2O2 concentration were 80gkg−1 and 10%, respectably. The graded modified Fenton’s oxidation with a 3-time addition of 10% H2O2 was able to remove 93.7% of total atrazine in the contaminated soil and maintain soil temperature within 50°C. In contrast to traditional Fenton treatment, a slight pH increase has been observed due to the addition of SCS. More importantly, experiment conducted at natural conditions with SCS gave the similar atrazine removal to the experiments with the other catalysts (e.g., FeSO4 and Fe2O3). One thing should be noted that after the treatment, dissolved organic carbon (DOC) content increased to 1.206gkg−1 from an initial value of 0.339gkg−1.
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