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br Introduction The protein Epidermal Growth Factor
2020-05-26

Introduction The protein Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR-TK) play important role in non small-cell lung carcinoma (NSCLC) and vital therapeutic progress withinin the treatment of this ailment has revamped the past ten years through the exploitation of this insight (Mok et a
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br Acknowledgments br Introduction Ubiquitin ligases limit
2020-05-26

Acknowledgments Introduction Ubiquitin ligases limit the stability and activity of substrates by targeting them for proteasomal-dependent degradation. Siah is a two-member family of ubiquitin ligases implicated in control of key cellular processes. Among those, Siah ligases control prolyl hydr
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In the context of E ligase drug
2020-05-26

In the context of E3 ligase drug discovery, it is critical to identify the appropriate E2/E3 substrate pairing to ensure the development and use of the most physiologically relevant screening assay. There have been many reports of limited E2/E3 activity profiling with a small number of E2 and E3 ddh
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Many studies reporting on discoveries
2020-05-26

Many studies reporting on discoveries of DUBs in the TGFβ and BMP pathways have relied on RNAi strategies to investigate loss-of-function impact. While RNAi strategies are useful tools, there are limitations ranging from limited knockdowns of targets to potential off-target effects. New and better t
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Two parameters were extracted from these experiments to
2020-05-26

Two parameters were extracted from these experiments to compare the interactions of the three compounds with ct-DNA. The association constant K for the binding of the naphthalimide derivatives to ct-DNA was calculated by fitting the evolution of the fluorescence spectra with a 1:1 binding model usin
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br Experimental Procedures br Acknowledgments The authors wi
2020-05-26

Experimental Procedures Acknowledgments The authors wish to thank P. Costet (University of Bordeaux) and Véronique Guyonnet-Duperat (FR TransBioMed, Plateforme de Vectorologie, University of Bordeaux) and Prof. Nils-Göran Larsson and Dr. Bettina Bertalan (Max Planck Institute for Biology of Ag
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br DGAT proteins lipid droplets and cancer cells
2020-05-26

DGAT proteins, lipid droplets and cancer cells Conclusions and future directions Conflicts of interest Acknowledgements This work was supported by NIH grants GM062887, P01CA097132, and Veterans Affairs Merit Award to LMO. Introduction Bioethanol and biodiesel are regarded as the two
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In untreated rodent or human hepatocytes PXR or
2020-05-26

In untreated rodent or human hepatocytes, PXR or CAR is stabilized by cytoplasmic co-chaperone partners like heat shock protein 90 (HSP90, Fig. 1). Upon ligand binding, the nuclear receptors are freed and translocated into the nucleus, identified as a pivotal step in PXR- or CAR-mediated transactiva
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Alvocidib flavopiridol is a piperidine
2020-05-26

Alvocidib (flavopiridol) is a piperidine-chromenone derivative (Fig. 6D) that is not FDA approved, but is in clinical trials for breast, endometrial, and several other cancers and hematological malignancies (Table 4) [[100], [101], [102], [103], [104]]. This drug targets CDK9 (IC50 = 3.2 nM) and CDK
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br Related work Goal of this
2020-05-26

Related work Goal of this section is to show related work focused on methods useful to assess the reliability of clustered COTS-based systems. Connelly et al. [1] propose an approach to delineate safety assurance for the use of COTS OS in safety-related applications, which must fall in SIL2. The
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As mentioned previously dopamine plays a
2020-05-26

As mentioned previously, dopamine plays a crucial role in reducing prefrontal cortical suppression to the amygdala (Rosenkranz and Grace, 2001) and prefrontal cortex mediated amygdala supression has recently been associated with vagal regulation of HRV (Sakaki et al., 2016). In addition, evidence ha
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Materials and methods br Results Assay of botulinum toxin ac
2020-05-25

Materials and methods Results Assay of botulinum toxin activity is critical for the risk-assessment, diagnosis, and treatment of botulism cases. The frequently encountered active forms of the toxin are; L chain (inside intoxicated neuronal cells), BoNT (in the blood stream of a botulism patient,
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serine protease inhibitor br Introduction Schistosomiasis on
2020-05-25

Introduction Schistosomiasis, one of the major parasitic diseases that affect humans in tropical and subtropical countries, is an acute and chronic condition caused by blood flukes (trematode worms) of the genus Schistosoma (World Health Organization, 2014). Schistosomiasis infects over 240 milli
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Our study provides proof of principle
2020-05-25

Our study provides proof of principle for dimerizing two different E3 ligases as a novel approach to inducing one ligase to degrade the other one. The outcome of ‘ligase versus ligase’ PROTAC-mediated activity might be unpredictable a priori, but could reveal a new mechanism for proximity-mediated h
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Several eukaryotic E enzymes including BRE RNF and
2020-05-25

Several eukaryotic E3 enzymes, including BRE1 [49], RNF8 [50], and RAD18 [24], [51], have been reported to partner with UBE2B in the ubiquitination of various targets. We examined the expression levels of these E3 enzymes in HONE1 and TW01 cells; RAD18 was highly expressed in these Myosmine mg (dat
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