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Collectively these data suggest the potential clinical utili
2019-12-27
Collectively, these data suggest the potential clinical utility of COMT inhibitors for the treatment of addiction disorders. Similar to current pharmacotherapies such as naltrexone, tolcapone\'s effects were not ethanol specific, therefore tolcapone may be effective in reducing other drug reinforced
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br Conclusions br Declaration of interest br Acknowledgment
2019-12-27
Conclusions Declaration of interest Acknowledgment This work was supported by an AIRC (Associazione Italiana Ricerca Cancro-Milan) Grant KFR062-2 to A.G.L, by Ricerca Funds by Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Grant No. 180/01) and by the ERA-NET “ERare” (Grant GO
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To develop antagonists selective for the
2019-12-27
To develop antagonists selective for the mouse EP1 receptor, we started with compound (), synthesized as previously described (). Diethyl dipicolinic Compstatin () was reduced with NaBH to . Parikh–Doering oxidation of with sulfur trioxide–pyridine complex and DMSO produced the unstable aldehyde
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br Structure of USP Schematic representation of
2019-12-27
Structure of USP7 Schematic representation of the USP7 domain architecture is shown in Fig. 3B. USP7 is a 135 kDa protein that consists of seven domains, including the N-terminal TRAF-like (Tumor necrosis factor Receptor–Associated Factor) domain, followed by the catalytic core domain and the fiv
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CYP A and CYP D
2019-12-27
CYP3A4/5 and CYP2D6 are among the main drug-metabolizing enzymes in humans that are responsible for the metabolism of more than 50% of marketed drugs [19], [21]. Drugs metabolized by CYPs are prone to drug–drug interactions, thereby modifying their response [18], [32]. Metabolic inhibition is also i
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The involvement of FOXO and STAT in DNA PKcs and
2019-12-26
The involvement of FOXO3 and STAT5 in DNA-PKcs and E3330 IV has not been reported before, and the search by the ECR browser (http://ecrbrowser.decode.org) revealed that 1kb of the 5′ promoter of DNA-PKcs possesses 4 STAT (−908bp to −901bp, −676bp to −656bp, −533bp to −526bp and −66bp to −59bp) and
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The overall poor outcomes in
2019-12-26
The overall poor outcomes in ESCC are thought because of a combination of late diagnosis, aggressiveness of the disease, and a lack of effective treatment strategies for systemic disease. Several molecular pathways, such as epidermal growth factor receptor, vascular endothelial growth factor, and p5
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Epac proteins consist of a carboxyl terminal
2019-12-26
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 a
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Protein ubiquitination occurs at the lysine residues
2019-12-26
Protein ubiquitination occurs at the lysine residues, and is mediated by the sequential reactions of ubiquitin-activating enzyme (E1), conjugating enzyme (E2), and ligase (E3). The first step in this process comprises the ATP-dependent activation of ubiquitin by E1 to form a ubiquitin–E1 conjugate.
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Within the X CX PX RX motif of
2019-12-26
Within the X1CX3PX5RX7 motif of several prokaryotic FGE substrates, the residues of X3, X5, and X7 are variably found as mixtures of alanine, glycine, threonine, or serine residues [26], [27]. The docked model of our identified HCTPRRP motif revealed that position X1 (H1) and position X7 (P7) were n
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In conclusion we demonstrate that
2019-12-26
In conclusion we demonstrate that infection of salmon cells with ISAV induce the main branches of the cellular UPR machinery, but also one of its main negative regulators, GADD34. This is probably important for maintaining translation of interferon and interferon stimulated genes (ISGs), keeping ISA
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This pre GC B cell
2019-12-26
This pre-GC B cell differentiation deficiency caused by RD2 loss of function was explained at least in part by the finding that the BCL6 RD2 domain is required to repress expression of the key migration factors GRP183 and S1PR1. Downregulation of GRP183 is critically important for B cell migration i
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Our previous studies indicate that EBI is
2019-12-26
Our previous studies indicate that EBI2 is involved in the regulation of pro-inflammatory responses and inter-cellular communication under pathophysiological conditions such as LPS challenge (Rutkowska et al., 2016b). The data showed that media taken from LPS stimulated astrocytes induces macrophage
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Many DNA repair pathways are candidates
2019-12-26
Many DNA repair pathways are candidates for DPC repair. Nucleotide excision repair (NER) is widely involved in both bacteria and eukaryotes in removing cross-linked protein with low molecular weights (11kDa) (Ide et al., 2011). The predominant pathway chosen by MRS 2179 tetrasodium salt may also dep
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Given the structural similarity of BMAA to other amino
2019-12-26
Given the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a previously unrecognised mechanism for BMAA action. Materials and methods Results and discussion We first examined whether chemical
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