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To study the role of DNA PK
2021-07-08

To study the role of DNA–PK in the response to replication arrest, we used the DNA replication inhibitor aphidicolin (APH). APH, a mycotoxin isolated from Cephalosporium aphidicola, inhibits DNA replication by interacting with the replicating DNA polymerase α (pol α). APH specifically inhibits the a
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The DNA damage response DDR is a
2021-07-08

The DNA damage response (DDR) is a cellular mechanism that protects against DNA damage induced by endogenous and exogenous factors, it includes changes in cellular processes such as mdm2 p53 regulation, DNA damage repair, apoptosis and chromatin remodeling. In recent years, the DDR has been recogni
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As a functional ETC is required for DHODH catalysis
2021-07-08

As a functional ETC is required for DHODH catalysis (Loffler, Jockel, Schuster, & Becker, 1997; Rawls, Knecht, Diekert, Lill, & Loffler, 2000; Zameitat, Freymark, Dietz, Loffler, & Bolker, 2007), DHODH depends on the mitochondrial ETC to generate adequate concentrations of ubiquinone (Fig. 2). Cells
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There was a good alignment profile between
2021-07-08

There was a good alignment profile between compound 26 (IC50 0.06μM) and MTX (IC50 0.08μM) explaining its activity pattern (Fig. 5a). Fig. 5b clearly indicates a different alignment profiles where carbonyl groups are not on the same side between 25 (IC50>100.0μM) and MTX which is in consistency with
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On the other hand the IL promoter activity induced by
2021-07-08

On the other hand, the IL-8 promoter activity induced by the signalling cascade of the CysLT1-G300S receptor is higher than that of the WT receptor. The chemokine IL-8 is mainly involved in the recruitment and activation of neutrophils and we have previously shown that this chemokine gene is a targe
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Tumor associated macrophages TAMs one of
2021-07-08

Tumor-associated macrophages (TAMs)—one of the limiting factors in anti-tumor immunity—are associated with the poor clinical outcome in most carcinomas, owing to their potential to promote angiogenesis and local invasion, increase the metastasis of tumor cells, and inhibit the anti-tumor immunity.11
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DLPC Placental insufficiency is regarded as
2021-07-08

Placental insufficiency is regarded as the main etiology for FGR. Placental development is highly unique in eutherians and is regulated by numerous factors. For example, the novel retrotransposon-derived gene retrotransposon-like 1 (RTL1) was recently shown to play a key role in placental developmen
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The reference standards methyl difluoro dioxolo benzo imidaz
2021-07-08

The reference standards methyl 3-((2,2-difluoro-5-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-]imidazol-6-yl)carbamoyl)benzoate () and -(2,2-difluoro-5-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-]imidazol-6-yl)-3-methoxybenzamide (), and their corresponding desmethylated precursors 3-((2,2-difluoro-5-[1,3]dioxolo[4′,5′:
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br In patients with type I diabetes mellitus
2021-07-08

In patients with type I diabetes mellitus poor management causes/INS; a drastic rise in glucose levels resulting in diabetic ketoacidosis (DKA). About 1% of DKA episodes can be complicated by cerebral edema. ET and its receptors are involved in the regulation of /INS;cerebral blood flow. We studie
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A possible explanation for these
2021-07-08

A possible explanation for these observations has been provided by a recent study showing that EWS-FLI-1 increases the Skp2-mediated 26S proteasome degradation, decreasing p27 protein stability and preventing cell senescence [42]. Mechanism of action of EWS-FLI-1 Molecular analysis has revealed
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Epac proteins consist of a carboxyl terminal
2021-07-08

Epac proteins consist of a carboxyl-terminal catalytic region and an amino-terminal regulatory region, which harbors one cAMP-binding domain in Epac1 and two in Epac2 [22], [32], [51]. In the absence of cAMP, the regulatory region covers the CDC25-homology domain and autoinhibits Epac's enzymatic ac
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In addition to the ESIs identified that target both
2021-07-07

In addition to the ESIs identified that target both EPAC1 and EPAC2, ESI-05 and ESI-07 were identified as compounds that selectively antagonise EPAC2, displaying almost no inhibition of EPAC1 at concentrations up to 100μM [99]. Both compounds were effective inhibitors EPAC2 GEF activity towards Rap1
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br Acknowledgements We thank Joseph Granger and Bryan Neuman
2021-07-07

Acknowledgements We thank Joseph Granger and Bryan Neumann for careful reading of this manuscript. This work is supported by NIH grants AG37609 and HL 60306 to TYC and CCYC. Introduction Eleven million tonnes of waste are produced yearly by the European pulp and paper industry (Monte et al.,
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Further indirect evidence supporting an important role
2021-07-07

Further indirect evidence supporting an important role of DPP-4 in the modulating the actions of both incretins comes from the observations that analogues of GLP-1 and GIP, modified to be resistant to DPP-4 cleavage, were subsequently shown to have greater metabolic stability in vivo which was assoc
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thyrotropin releasing hormone br Discussion The biochemical
2021-07-07

Discussion The biochemical separation of exonuclease activity from DNA-PK dependent endonuclease activity reported in this manuscript is consistent with genetic separation of Artemis enzymatic activity. Mutations in the protein which result in disruption of endonuclease activity have no effect on
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