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To study the role of
2021-02-10

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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br Introduction Coping with DNA damage is possible thanks
2021-02-10

Introduction Coping with DNA damage is possible thanks to surveillance mechanisms (checkpoints), that detect the problem and promote its solution [1], [2], and to repair and tolerance pathways that remove the lesions or reduce the damage consequences [3], [4]. Failures in these processes have a h
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The only in vivo evidence
2021-02-10

The only in vivo evidence for a role of DDR2 in fibrotic disease showed that DDR2 knockout mice exhibited exaggerated severity of chronic hepatic fibrosis. Although a previous in vitro study has demonstrated that DDR2 promotes lung fibroblast proliferation and migration, till now it remains unclear
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src kinase inhibitor Although the crystal structures of Atg
2021-02-10

Although the crystal structures of Atg4C and Atg4D are not available, their three dimensional structures can be acquired by homology modeling, using the structure of Atg4B as a template (Zhang, Li, Ouyang, Liu, & Cheng, 2016). In that model, the catalytic triad is conserved (Cys110/Asp345/His347 for
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Natural and synthetic glucocorticoids perform
2021-02-10

Natural and synthetic glucocorticoids perform their biological action in the organism through receptor-dependent mechanisms (e.g., by binding to the glucocorticoid receptors). It has been determined that glucocorticoid receptors cross-talk with other nuclear receptors, including AhR (Celander et al.
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The secondary objective of the present study was
2021-02-10

The secondary objective of the present study was to evaluate the pharmacokinetics, safety, and tolerability of multiple oral doses of 450-mg delafloxacin to reach steady state in healthy male and female subjects. After multiple dosing of oral delafloxacin, steady state was reached after 4 days of do
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Previously to detect CDKL activity we
2021-02-10

Previously, to detect CDKL5 activity, we used a radioactive phosphorylation assay with amphiphysin 1 protein as a substrate [,,]. However, it is necessary to establish a safe and rapid method for analyzing CDKL5 mutant activity. Here, we report a new method for investigating autophosphorylation acti
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First we synthesized inhibitor following the patent procedur
2021-02-10

First, we synthesized inhibitor following the patent procedure reported by Shewchuk et al. to provide its first complete characterization (see ). Two different synthetic approaches were used to obtain compounds –. The first method relied on the alkylation of the common 5-phenol-2,4-diaminopyrimidin
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The P H activity and the large number
2021-02-10

The P4H activity and the large number of 4-Hyp residues that are formed, amounting to half of all the Pro residues or 10% of all residues, have been identified as having a clear role in the structure and chemistry of the triple helix [3]. The role of the rare 3-Hyp residues is less clear and is stil
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br Acknowledgments br Introduction Cholesterol is an essenti
2021-02-10

Acknowledgments Introduction Cholesterol is an essential lipid for the development, growth, and wellbeing of humans. In newborn children, cord blood cholesterol concentration is 1.5 mmol/l, on average [[1], [2], [3], [4]]. During the first year of life, cholesterol concentration in serum incre
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br Membrane receptor Indirect non genomic signaling As
2021-02-09

Membrane receptor: Indirect non-genomic signaling As mentioned above, not all protease inhibitor responses fit the classical genomic model of steroid action. The observation of excessively fast estrogen-induced biological responses led to the development of the hypothesis that estrogen could be
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In this study we also conducted an analysis
2021-02-09

In this study, we also conducted an analysis comparing the expression profiling of Hh genes among the sarcomas investigated. In these tumors, the IHH gene showed a higher expression level than PTCH1 gene in RMS and SS samples (pGSK1324726A in human RMS cell lines as well as mouse NIH-3T3 fibroblasts
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Prostaglandins PGs in particular PGE
2021-02-09

Prostaglandins (PGs), in particular PGE2 and PGF2α, play pivotal roles in human parturition by stimulating cervical ripening, myometrial contraction and fetal membrane rupture (Challis et al., 1997). In human pregnancy, the amnion is the principle source of PGE2 (Duchesne et al., 1978). In the amnio
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br Concluding remarks and prospective Cardiac proteinopathy
2021-02-09

Concluding remarks and prospective Cardiac proteinopathy, a more common disease condition and more frequent cause of cardiomyocyte decay than previously thought, is largely neglected and no effective therapy exists yet. Protein quality control and protein degradation via autophagy or the ubiquiti
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Crystallographic and NMR based analyses have
2021-02-09

Crystallographic and NMR-based analyses have revealed that RINGs and U-boxes have a common mode of interaction with E2s (Fig. 2A). The key structural elements are two loop-like regions, which, in the case of RINGs, coordinate Zn. The loops surround a shallow groove formed by the central α-helix. Tog
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