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br Mechanisms of acquired resistance to
2019-09-19
Mechanisms of acquired resistance to 1st and 2nd generation EGFR inhibitors After treatment with first or second generation EGFR TKIs, virtually all patients after approximately 12 months develop acquired resistance (AR). Different mechanisms of AR to EGFR TKIs have been reported to date and may
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Overall the evidence and the results
2019-09-19
Overall, the evidence and the results from in vivo studies clearly indicate that cyclosporine biotransformation can be induced by dasatinib co-administration through induction of CYP3A expression. However, further studies are needed to explore the role of P-gp modulation in DDIs. Conclusion In v
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Our finding that the ATRX DAXX H complex
2019-09-19
Our finding that the ATRX-DAXX-H3.3 complex promotes a form of HR is likely to have important implications for our understanding of the ALT recombination process that takes place at telomeres. We were surprised to observe that ATRX promotes a form of HR, since loss of the ATRX-DAXX-H3.3 complex is n
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In conclusion high methylation levels of CDKL were observed
2019-09-19
In conclusion, high methylation levels of CDKL2 were observed both in HCC cell lines and tissues, which showed a negative association with mRNA expression. Moreover, treatment with demethylation agent in HCC cell lines could upregulate CDKL2 mRNA expression. The discovery of the epigenetic modificat
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Experiment Blunted fear potentiated startle due to deficient
2019-09-19
Experiment 2: Blunted fear-potentiated startle due to deficient fear acquisition. SERT+/+ and SERT+/− showed significant acquisition of the cue-shock association, whereas SERT−/− did not (trial×genotype interaction: F2,50=3.3, pPicrotoxin mass of fear-potentiated startle. Acquisition: Following f
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Like all other cellular processes ubiquitination is
2019-09-18
Like all other cellular processes, ubiquitination is also tightly regulated; more so, as myriads of pathways are controlled via this conjugation and dysregulation of ubiquitination has been implicated in various diseases including cancer [16], [17]. Quite a few of such regulatory mechanisms that con
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br E mediated E discharge E ligases simultaneously interact
2019-09-18
E3-mediated E2 discharge E3 ligases simultaneously interact with the substrate and the SUMOD charged E2 enzyme to catalyze the discharge of the thioester-bound SUMOD from the E2 to the substrate. E3 interaction with SUMOD via a SIM results in a closed conformation which is highly reactive and lea
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The expression of cytokine inducible genes is
2019-09-18
The expression of cytokine-inducible genes is mediated by a number of components within the cell. It has been shown that Jak2 and the Ras/Raf/MAP kinase signaling cascades are required for the expression of DUB-1[9], [29]. However, the enhancer domain of DUB-1 lacks a consensus sequence for Stat bin
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Classical DHFR inhibitors such as methotrexate MTX bind tigh
2019-09-18
Classical DHFR inhibitors such as methotrexate (MTX) bind tightly to the enzyme and possess adequate clinical pharmacokinetics. MTX bind to the DHFR binding site through the formation of hydrogen bonds with Asn64, Lys68, Arg28, Arg70, Val115 and Ile7 amino NSC 319726 kinase residues as well as hydr
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br Results On the th day the
2019-09-18
Results On the 8th day, the horizontal (Fig. 1) and vertical locomotor activity (Fig. 2) and the dorsal (Fig. 3) and PF 04418948 striatal dopamine release (Fig. 4) increased significantly in nicotine-treated rats, compared with the saline-treated rats. Tukey post-hoc test revealed the following p
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The performance of the qCPA approaches is similar with regar
2019-09-18
The performance of the qCPA approaches is similar with regards to the derivative properties of CO2 and for mixtures of CO2+self-associating compounds. For CO2+n-alkanes the four-parameter versions of qCPA both perform somewhat better than the three-parameter version. Nevertheless this modest improve
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In some pancreatic and non pancreatic tissues the chloride a
2019-09-18
In some pancreatic and non-pancreatic tissues, the chloride and calcium channels are heavily regulated by phosphorylation by protein kinases, such as PKC, cyclic AMP-dependent protein kinase (PKA), PKCaMKII, PI3K and protein tyrosine kinases [7,36,37]. Since the interaction of triterpenes with recep
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br Conclusion br Acknowledgments This work was supported
2019-09-18
Conclusion Acknowledgments This work was supported by Progetto PON - “Ricerca e Competitività 2007–2013” - PON01_01802: “Sviluppo di molecole capaci di modulare vie metaboliche intracellulari redox-sensibili per la prevenzione e la cura di patologie infettive, tumorali, neurodegenerative e lor
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Several studies have shown that independently
2019-09-17
Several studies have shown that, independently of body-weight control, the central actions of leptin improve glycemic control in obese diabetic rat and mouse models [62]. For instance, restoration of OB-Rb expression in OB-Rb-deficient mice, and in particular in POMC neurons, was sufficient to norma
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COH inhibited global SUMOylation in cells
2019-09-17
COH000 inhibited global SUMOylation in voltage gated potassium channel and blocked the E1 catalyzed attachment of SUMO to the corresponding conjugating enzyme Ubc9, but not the attachment of ubiquitin or NEDD8 to their respective E2s, confirming inhibition and specificity in cellulo. Consistent with
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