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Previously we had proposed three
2021-02-02

Previously we had proposed three possible models, with one being that hCrm1 fundamentally interacted more favorably or strongly with Rev-RRE complex, compared to mCrm1. We decided to test that model, which was the simplest and most straightforward, by both biochemical and genetic means. By using bac
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To investigate the mechanism of action
2021-02-02

To investigate the mechanism of action of 2,4,5-trisubstituted azoles, we profiled selected 2,4,5-trisubstituted azoles against a panel of 97 kinases to identify potential targets that could be involved in cardiogenesis. We narrowed down the identified targets to the casein kinase 1 (CK1) family due
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Since the dideoxy analogues and
2021-02-02

Since the 1,2-dideoxy analogues, and , served as substrates for TgTCEA and TgTCEB, respectively, with the higher affinity (lower ) and lower turnover number (lower ) than their authentic substrates, PosA and PosB (such trend was more evident on analogue for TgTCEB than on analog for TgTCEA), an i
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br Conclusion The present study
2021-02-02

Conclusion The present study is the first to provide in vivo evidence that the σ1R deficiency can cause age-related increases in aggregation and phosphorylation of αSyn in dopaminergic neurons of SNpc. The σ1R has been reported to be decreased in the AACOCF3 region of the nigrostriatal dopaminer
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br Results br Discussion Our UbV library was
2021-02-02

Results Discussion Our UbV library was originally designed to develop inhibitors of deubiquitinases (Ernst et al., 2013). Recently, we showed that UbVs could exhibit multiple binding modes and mechanisms to modulate HECT E3 activity (Zhang et al., 2016)—one set occupied the HECT domain E2-bind
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Increased levels of PCNA monoubiquitination by UbL P express
2021-02-02

Increased levels of PCNA monoubiquitination by UbL73P expression in a damage-independent manner mimics the phenotype observed for USP1 knockdown (Huang et al., 2006, Jones et al., 2012). USP1 is the only DUB to date shown to remove ubiquitin from PCNA in vivo. This finding reveals the highly dynamic
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As a functional ETC is
2021-02-02

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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br Results br Discussion The structures
2021-02-02

Results Discussion The structures presented here were solved at high MCC950 sodium and show in detail how DDR1 achieves high affinity for imatinib and ponatinib, respectively. Both type II inhibitors bind in their more potent extended conformations to the inactive DFG-out conformation of the k
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br Materials and methods br Results and discussion
2021-02-01

Materials and methods Results and discussion Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases [28], [29] catalyze oxidative reactions of a range of metabolic processes including the hydroxylation of l-proline and l-lysine residues during the post-translational modification of collagen. Mor
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Immune modulation by steroid hormones is
2021-02-01

Immune modulation by steroid hormones is a rather new aspect of the research on endocrine interactions in lower vertebrates (Harris and Bird, 2000). In the classical view, steroids exert their effects by binding to specific intracellular receptors that function as ligand-activated transcriptional re
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Additionally although the membrane localized ER signaling de
2021-02-01

Additionally, although the membrane-localized ER signaling described in this review has generally been studied in isolation from nuclear signaling, it is becoming clearer and clearer that integration of these mechanisms must be considered (Frick, 2015). Perhaps the distinct estradiol signaling mecha
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Metal ions are known not to
2021-02-01

Metal ions are known not to be necessary for catalytic activity of serine proteinases. Nevertheless, Co2+ and Ca2+ ions were found to stabilize glutamyl endopeptidase molecule [1], [7], [19]. In our previous study, we have described significant stimulating effect of Ca2+, Mg2+, and Co2+ on biosynthe
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Introduction Cholesterol plays a pivotal role
2021-02-01

Introduction Cholesterol plays a pivotal role as a constituent of biological membranes and as a precursor for vitamins, hormones and bile acids. Accordingly, its production, distribution, and elimination must be tightly regulated at the cellular and organismal level. Accordingly, dysregulated chole
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Historically covalent drugs have had great success e
2021-02-01

Historically, covalent drugs have had great success (e.g., aspirin and penicillin), and covalent drugs have become a focus in anticancer and antiviral drug discovery (Kalgutkar and Dalvie, 2012, Singh et al., 2011). These compounds contain low reactivity warheads that allow covalent adducts to form
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Because macrophages clear the injured tissue
2021-02-01

Because macrophages clear the injured tissue of dead mst1 kinase and matrix debris, macrophage infiltration is essential for normal tissue repair. In cardiac remodeling by MI, however, macrophages infiltrate excessively into not only the infarct area and marginal area of MI. Infiltrated macrophages
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