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In conclusion our work provides the preclinical evidence sho
2019-09-21

In conclusion, our work provides the preclinical evidence showing the potent in vivo efficacy of AT7519 on chemoresistant cancer TCS PIM-1 1 and its underlying mechanisms of action. Our work supports the biological rationale behind the clinical trials initiated with AT7519, particularly for the tre
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CXC chemokines are primarily expressed in immune
2019-09-21

CXC chemokines are primarily expressed in immune organs and the central nervous system: the mouse thymus and spleen (Heesen et al., 1996), chicken bursa (Liang et al., 2001), primate (Macaca mulatta) acpt and (Federsppiel et al., 1993) and cattle locus coeruleus, cerebellum and pons (Rimland et al.
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GS-4997 and br Materials and methods br Results
2019-09-20

Materials and methods Results Discussion It has been demonstrated that up-regulation of EPHB4 impaired trophoblast migration and invasion during placentation, which may contribute to the pathogenesis of preeclampsia [11], [24]. However, the upstream regulating mechanism of EPHB4 expression
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Our results indicate an OT specific activation of
2019-09-20

Our results indicate an OT-specific activation of PKR that inactivates eIF2a and may, by this means, reduce protein translation by utilizing only select sensors and mediators of the UPR (i.e., avoiding significant PERK activation). Interferon is a PKR activator [32] that temporarily subdues cellular
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br Results br Discussion Taking
2019-09-20

Results Discussion Taking advantage of the highly specific protein–protein interactions among cognate BX-912 and that mediate SUMO conjugation to substrates, we have developed a novel strategy for achieving inhibition of SUMO conjugation in vivo based on disruption of SUMO E1–E2 interactions.
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There is a functional ubiquitin
2019-09-20

There is a functional ubiquitin association (UBA) domain at the N terminus of MCPIP1. Liang et al. have discovered that MCPIP1 may be a deubiquitinase and defined a novel DUB domain of MCPIP1 [22]. Ubiquitin and deubiquitin modification emerge as the key mechanisms that regulate the virus-induced ty
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br Acknowledgements We thank Jeffrey D Konowalchuk and John
2019-09-20

Acknowledgements We thank Jeffrey D. Konowalchuk and John Sony Robbins for their technical assistance. This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) grants to DRB (RGPIN-2013-355303) and MB (RGPIN-2014-96395). AMR was supported by NSERC Vanier Doct
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br Genomic and non genomic signaling
2019-09-20

Genomic and non-genomic signaling crosstalk As exemplified in the previous sections, it is evident that the mechanisms of action of estrogen in the various cell targets represent a combination of complex multifactorial processes. Besides the independent genomic and non-genomic pathways described
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br A major physiological action of
2019-09-20

A major physiological action of ET-1 is to function as one of the most powerful vasoconstrictors of human blood vessels. As such, ET-1 plays a major role in regulating vascular function in all organ systems, including the kidney (Fig. 1). As in other vessels, ET-1 is thought to be released from en
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br Introduction Esophageal squamous cell carcinoma
2019-09-19

Introduction Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in East Asia and is a leading cause of cancer-related death worldwide.1, 2 Surgery is widely used for treatment in localized disease, where it can provide definitive management and potential cure. Tre
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In all available E E structures
2019-09-19

In all available E2:E3 structures, the RING-type domain binds the E2 on a surface that is remote from the active site Cys (and therefore from the ubiquitin thioester) (Fig. 2). The non-contiguous E3-binding and active sites on the E2 imply that the role played by a RING to facilitate ubiquitin trans
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br Results br Discussion Previous studies have mapped ABCF a
2019-09-19

Results Discussion Previous studies have mapped ABCF1 as a risk factor gene for rheumatoid arthritis and autoimmune pancreatitis (Ota et al., 2007, Richard et al., 1998). Additionally, recent genome-wide association studies have also associated ABCF1 with the risk of gout (Dong et al., 2017) a
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One of the critical functions of the product
2019-09-19

One of the critical functions of the product of the AR gene is to activate the expression of target genes. This transactivation activity resides in the N-terminal domain of the protein encoded in exon 1, which contains polymorphic repeats. These trinucleotide repeats, (CAG) and (GGC), encode polyglu
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comt inhibitors The positive correlation between ATG and DCT
2019-09-19

The positive correlation between ATG7 and DCTPP1 (TCGA data) suggested our hypothesis that DCTPP1 may affect the phenotype of prostate tumor, or maybe other types of tumors as well, through its role in autophagy. To test this hypothesis, we carried out western-blot experiments in which the ratios of
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The present study provides the first
2019-09-19

The present study provides the first evidence that the human uroepithelial membrane transport in vitro respond directly, within 48h, to this carcinogen by promoting extensive vacuolation and DAPK expression. By using the TEM, ICC and Western blotting, we found that the arsenite-induced vacuoles were
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