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van Linden et al developed a comprehensive guide
2019-08-27
van Linden et al. developed a comprehensive guide that describes drug and ligand binding to more than 1200 human and mouse protein kinase domains [77]. Their KLIFS (kinase–ligand interaction fingerprint and structure) directory includes an alignment of 85 potential ligand binding-site residues occur
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In our model CSF R blockade
2019-08-27
In our model, CSF-1R blockade with PLX647 mainly targeted the more abundant MDSCs instead of macrophages, suggesting that the role of CSF-1 may be tumor model-dependent. Different tumor models, genetic backgrounds, or treatments may induce different growth factors or cytokines in the tumor microenv
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Our results indicate that C
2019-08-27
Our results indicate that C75-CoA is formed in the hypothalamus following stereotaxic injection of C75. Inhibition of hypothalamic CPT1 by C75-CoA in vivo, as seen in our experiments, is independent of the putative inhibition by malonyl-CoA, which may be formed after the action of C75 either on FAS
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Allele specific methylation has been observed in CpG
2019-08-27
Allele-specific methylation has been observed in CpG islands of imprinted genes.27, 32 In the present study, however, methylation of CpG1 was specific to ALL UCM05 and occurred in the leukemia cells of 28% of children with ALL, but it was not found in normal leukocytes from the same patients. Methy
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Activating GSK signaling to inhibit PK
2019-08-27
Activating GSK3β signaling to inhibit PK signaling during ischemia/reperfusion (I/R) is protective of WM ischemic injury. Glycogen synthase kinase (GSK3), which was the first substrate identified for AKT [44], is inhibited by AKT phosphorylation at positions S9 and S21 [45]. When GSK3β is active, it
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Current therapeutic protocols in OS and
2019-08-27
Current therapeutic protocols in OS and ES consist of neoadjuvant chemotherapy and local surgical resection, followed by adjuvant chemotherapy. These treatments lead to a 70% overall survival for localized disease but can decrease to 15% in case of metastasis. With CS being resistant to conventional
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Cobimetinib and br Conclusions br Declaration of
2019-08-27
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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Herein we further established a dynamic DNA
2019-08-27
Herein, we further established a dynamic DNA self-assembly activated hemin-mimetic enzymes system by embedding DNA-hemin into an entropy-driven DNA-assembly for fluorescent biosensing. The entropy-driven dynamic DNA-assembly is one of the toehold-mediated isothermal strand displacement reactions, wh
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The potential existence of ER stress was first examined in
2019-08-27
The potential existence of ER stress was first examined in EVTs in placental bed biopsy specimens obtained from pregnancies complicated by early-onset preeclampsia. It was then tested whether ER stress can modulate MMP-2 activity before elucidating the role of proinflammatory cytokines in the induct
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The authors identified inhibitors of SUMOylation using two a
2019-08-27
The authors identified inhibitors of SUMOylation using two assays to monitor the conjugation of SUMO1 to RanGAP1 by E1 and E2 enzymes: a fluorescence resonance energy transfer (FRET) primary screen that evaluated over 250,000 compounds and a chemiluminescence secondary screen. A counter screen was u
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pterostilbene pathway br Future perspectives Understanding h
2019-08-27
Future perspectives Understanding how peptides are degraded, particularly those which may be therapeutically useful, such as GLP-1, has proved to be invaluable in providing a rationale for the development of a novel class of therapeutic agents. However, while DPP-4 plays an important role in the
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In addition to cleaving ubiquitins off modified proteins
2019-08-27
In addition to cleaving ubiquitins off modified proteins, DUBs can also cleave between ubiquitin moieties within a polyubiquitin chain to edit the ubiquitin signal. DUBs employ different strategies to recognize polyubiquitin (Figure 1). DUBs that rely only on interactions on the S1 site tend to be L
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br Experimental Procedures br Author Contributions br
2019-08-26
Experimental Procedures Author Contributions Acknowledgments Introduction Breast cancer is one of the most common malignancies for women worldwide, representing approximately 22% of women’s malignancies that pose a threat to women’s health [[1], [2], [3], [4]]. The morbidity rate of brea
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In this study Oncomine GEO and TCGA databases were used
2019-08-26
In this study, Oncomine, GEO and TCGA databases were used to analyze the expression of UBE2S gene in HCC and normal liver tissues to determine the relationship between UBE2S expression and prognosis of hepatocellular carcinoma. The potential function of UBE2S in HCC was analyzed by screening UBE2S c
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Thus DGK active sites remain
2019-08-26
Thus, DGK-active sites remain ill-defined and, combined with the lack of crystal structures for mammalian DGKs, have limited our understanding of substrate and inhibitor binding. As a result, current DGK inhibitors consist of compounds with poor specificity within the DGK superfamily (de Chaffoy de
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