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Mild cognitive impairment MCI is a clinical transitional sta
2020-11-28

Mild cognitive impairment (MCI) is a clinical transitional stage between normal aging and Alzheimer disease (AD) [1]. Approximate 15–30% MCI patients convert to AD annually. Although many efforts have been taken to prevent the conversion from MCI to AD [2], [3], there are few biomarkers to predict t
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In the present study we did not
2020-11-28

In the present study, we did not examine whether the CpG site-specific COMT methylation are associated with any genetic variants in response to E2, GEN or SFN. Some studies suggest that oxidative DNA damage causes genetic variation which may induce epigenetic changes that lead to gene silencing (Kho
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Emi protein consists of an N
2020-11-27

Emi2 protein consists of an N-terminal regulatory region and a C-terminal functional region. The C-terminal region contains a destruction box (D-box), which likely competes with APC/C substrates (including cyclin B) for APC/C binding, and a zinc-binding region (ZBR), which somehow inhibits APC/C ubi
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This study was aimed to assess a number of esterase
2020-11-27

This study was aimed to assess a number of esterase activities, namely erythrocyte AChE, plasma BuChE and BeChE, and serum PON1 towards a number of substrates, as well as the major genetic polymorphisms of BCHE and PON1in a cohort of greenhouse workers exposed to low toxicity pesticides under an int
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br Results br Discussion The advent of TKI treatment has
2020-11-27

Results Discussion The advent of TKI treatment has greatly improved CML therapy. Because CML LSCs are less sensitive to TKIs, CML is usually controlled rather than cured, highlighting an unmet clinical need. Developed from our previous finding that CML LSCs are more dependent on Tcf1 and Lef1
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br Disclosure statement br Acknowledgements This
2020-11-27

Disclosure statement Acknowledgements This research was supported by grants from the National Institutes of Health, NS046400 and AG022971 (SD), and a fellowship from the Korea Research Foundation, KRF-2007-357-E00016 (YTK). The authors thank Dr. Barbara Crain for assistance with the immunologi
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In conclusion we have identified Ednra as a
2020-11-27

In conclusion, we have identified Ednra as a downstream direct target of Hoxa9 and Meis1. Upregulation of Ednra has a role in the progression of Hoxa9+Meis1-induced leukemia and targeting Ednra together with other chemotherapies may have therapeutic benefits for leukemia [30]. Ednra inhibitors in th
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Each of these substrate receptors belongs to a multigene fam
2020-11-27

Each of these substrate receptors belongs to a multigene family with tens, if not hundreds of members in plants, and with in part overlapping and in part differential substrate specificities [4]. The complexity of the system is nicely illustrated by the F-box protein and auxin receptor TRANSPORT INH
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Despite the fact that the precise relevance
2020-11-27

Despite the fact that the precise relevance of Ube2E self-ubiquitination in vivo is still elusive, findings of Sarkari et al. do establish Ube2E1 ubiquitination in Furosemide synthesis [36]. In vivo self-ubiquitination of Ube2E1 is further supported by the high-throughput study aimed to identify al
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Programmed cellular death or apoptosis is
2020-11-27

Programmed cellular death or apoptosis is a process genetically controlled that plays an important role in cellular homeostasis, being an important defense mechanism to remove cells that have been infected, damaged or mutated (Smith and Smith, 2012, Wlodkowic et al., 2011). Nevertheless, apoptosis s
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During the past three decades platinum
2020-11-27

During the past three decades, platinum-based DNA-alkylating agents have been employed in the treatment of various cancers [14]. Oxaliplatin is currently used as a first-line treatment for colorectal cancer (CRC) [15]. Unfortunately, a large portion of CRC patients receiving oxaliplatin-based chemot
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br Conformational properties of DGK br Interaction of DGK wi
2020-11-27

Conformational properties of DGKϵ Interaction of DGKϵ with its lipid substrate A major component of the interaction between DGKϵ and lipid bilayers is the insertion of the hydrophobic segment comprising residues 20–42 into the membrane, as discussed above. However, this is not the only interac
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br Acknowledgments We thank Jon Clardy
2020-11-27

Acknowledgments We thank Jon Clardy, Juan Manuel Domínguez, José Francisco García Bustos, and the GlaxoSmithKline (GSK) Plasmodium falciparum dihydroorotate dehydrogenase project team for their contributions, helpful advice, and discussions. Introduction Dihydroorotate dehydrogenase (DHODH) i
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In conclusion we have discovered two new derivatives and
2020-11-27

In conclusion, we have discovered two new derivatives ( and ) that are potent inhibitors of DHODH. H and C NMR spectroscopic data revealed that these compounds undergo ready isomerisation at room temperature in -DMSO, but the docking studies indicate that there is neither conformation nor configurat
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Mitochondrial depolarization induced by DHODH inhibition Fig
2020-11-26

Mitochondrial depolarization induced by DHODH inhibition (Figure 5A) may also contribute to the selective effects of DHODH inhibitors on KRAS mutant cells. If so, the effect may arise more from pro-apoptotic effects of mitochondrial depolarization (Lemasters et al., 1998) than from impaired oxidativ
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