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The folate pathway plays an
2020-08-28
The folate pathway plays an essential role in cell survival by generating 5, 10-methylene tetrahydrofolate as a one-carbon donor for the synthesis of deoxythymidine monophosphate (dTMP), purines, methionine and histidine. Disruption of this pathway leads to the critical deficiency of these key molec
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NG25 In this study we further investigated the involvement o
2020-08-28
In this study, we further investigated the involvement of CRF1 and CRF2 receptors of the dPAG in the regulation of panic-related responses. For this, we used two animal models that associate escape behavior with panic attacks: the elevated T maze and the electrical stimulation of the dPAG (for a ful
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A An optimized BEI SEIscore based on
2020-08-27
(A) An “optimized BEI-SEIscore” based on the trends, emerged from the statistical analysis of several optimization studies in pharmaceutical industry (Abad-Zapatero, 2007, Abad-Zapatero and Blasi, 2011). This type of optimized scores has been used in many previous studies. Ki=1nM at 300° K, compare
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Almost of drugs in the market undergo
2020-08-26
Almost 75% of drugs in the market undergo deactivation though oxidation, reduction or hydrolysis by cytochrome P450 (CYP) enzymes, and then, either directly or by facilitated excretion from the body (Guengerich, 2008). The CYP3A subfamily is of particular interest because of its broad substrate spec
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Proteins that associate to PCNA
2020-08-26
Proteins that associate to PCNA are characterized by having conserved motifs as the PCNA-interacting protein (PIP) motif [29,30], its variant PIP-like motif [31,32] or the APIM motif (Alk B homologue 2 PCNA interacting motif [33,34]); for instance, p21 contains a PIP motif [30], and DNA polymerases
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The effect of the simple
2020-08-26
The effect of the simple dopaminergic tonic/phasic model on cognitive processing has been investigated by a few studies (Nolan et al., 2004; Rosa et al., 2010). Rosa et al. (2010), using a Stroop task that requires different levels of cognitive flexibility and stability, observed an association betw
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The cholinergic system has been shown to play a
2020-08-26
The cholinergic system has been shown to play a role in regulation of the inflammatory response [13] as well as in the influence of the metabolism of PCa cells [14]. The reduced activity of cholinesterase (ChoE) and the consequent increased amount of abscisic acid has been shown to lead to a cholin
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All components of the UPP were predicted to be susceptible
2020-08-26
All components of the UPP were predicted to be susceptible to oxidative stress due to the cysteine residues in their active sites [36]. Curcusone D inhibits DUBs but has no significant effect on the action of E1, E2s, E3s, or the proteasome, which indicates that the targets of the ROS induced by cur
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Treatment related adverse events have
2020-08-24
Treatment-related adverse events have been a serious issue in clinical application. Severe toxicity has been reported in clinical trials using antibody blockade of CSF-1R (20 mg/kg), PD-1, and CTLA-4.29, 30, 31 However, apparent side effects were not observed in our study with PLX3397 treatment alon
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Gramine br Acknowledgements We are grateful to the National
2020-08-24
Acknowledgements We are grateful to the National Natural Science Foundation of China (Grant Nos. 21571033 and 81503099) and the New Drug Creation Project of the National Science and Technology Major Foundation of China (Grant No. 2015ZX09101032) for financial aids to this work. The research was a
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Nevertheless because of the preclinical
2020-08-24
Nevertheless, because of the preclinical work and the interference with EWS–FLI1 transcriptional activity, we believe that there may be a role for ET-743 in Ewing sarcoma. An analysis of the pharmacokinetic data published in the phase II clinical trial shows that at most the drug spent 5 to 6days ou
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br Conflicts of interest br
2020-08-24
Conflicts of interest Acknowledgements This work was supported, in part or in whole, by the grants from the National Natural Science Foundation of China (11802056, 11772088), the China Postdoctoral Science Foundation (2018M640904), and the Fundamental Research Funds for the Central Universitie
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In conclusion we propose that UBE T FANCT
2020-08-24
In conclusion, we propose that UBE2T (FANCT) mutations define a FA subtype. This is also a rare example of a mutated E2 enzyme causing an inherited human disorder, like UBE2A. The p.Gln2Glu substitution is probably hypomorphic, as indicated by the fact that a siUBE2T knockdown made AP65P-hTERT mek i
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Atg cleaves Atg at the peptide bond on the glycine
2020-08-24
Atg4 cleaves Atg8 at the peptide bond on the glycine residue at the C-terminus, thus allowing the conjugation of Atg8 to phosphatidylethanolamine (PE) with the participation of other autophagy molecules. Atg4 can also serve as a deconjugating enzyme, which cleaves the amide bond of the conjugated At
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We also evaluated the influence of
2020-08-24
We also evaluated the influence of the number of CYP3A variant Propidium iodide (n=0 to 3) on the modifying effects on MDI and PDI. No clear allele dosage effect could be observed (data not shown). Discussion Prior reports for all four populations showed that an increase in prenatal Hg was not
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