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br Rationale and hypothesis To discover an
2020-12-17
Rationale and hypothesis To discover an allosteric inhibitor of EGFR, Jia et al. (2016) screened a library of 2.5 million compounds at 1 μM ATP concentration in opposition the purified EGFR L858R/T790M mutant enzyme. 1322 best hits were found from this round of screening. The pinnacle hits had be
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Immunomodulation effects of certain oxysterols were previous
2020-12-16
Immunomodulation effects of certain oxysterols were previously shown to depend on activation of oxysterol-binding liver X receptors (LXRs). Recent work from our labs as well as from others has shown additional receptors linking oxysterols and immunity. For example, we found that 7α,25-dihydroxychole
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In addition to tissue resident stromal and
2020-12-16
In addition to tissue-resident stromal and myeloid cell populations, ILCs also readily engage in positive-feedback loops with myeloid difluprednate australia recruited from the circulation. TNF-α produced by inflammatory monocytes recruited to the lungs of mice infected with Klebsiella pneumoniae ma
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Intriguingly one E residue may serve as a molecular gate
2020-12-16
Intriguingly, one E2 residue may serve as a molecular ‘gate’ to allow the C-terminus of ubiquitin to access the closed E2~Ub conformations favorable for ubiquitin transfer. This residue, Asp87 in UbcH5 family members, resides on one side of the opening that leads to the active site Cys (Fig. 4D). In
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A second advance came with the discovery that conformational
2020-12-16
A second advance came with the discovery that conformationally-flexible benzamide analogs having an N-phenylpiperazine moiety possessed good affinity and modest selectivity for D3 versus D2 receptors [3,[14], [15], [16]]. This observation spawned a significant effort by medicinal chemists to develop
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The biological significance of DNA ligases is
2020-12-16
The biological significance of DNA ligases is attributed to their function in DNA replication, recombination and/or DNA repair [1], [2]. In vertebrates, three different DNA ligases I, III and IV are recognized. DNA ligase I is essential for the Okazaki fragments’ ligation during lagging-strand DNA s
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br Acknowledgements br Introduction Lung cancer treatment st
2020-12-16
Acknowledgements Introduction Lung cancer treatment strategies, especially molecular targeted therapy, have progressed rapidly. However, most established treatments are for adenocarcinoma of the lung, not for squamous cell carcinoma (SQCC). SQCC constitutes approximately 30% of lung cancers, w
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TPPU Findings from this study also indicate that DAPK regula
2020-12-16
Findings from this study also indicate that DAPK regulated BimEL expression during OGD as DAPK shRNA transfection inhibited OGD-induced increase of BimEL. A previous study shows that Bim is found in ER compartment in stressed TPPU but not in normal cells, indicating translocation of Bim during ER st
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In vivo study showed that the CYP A activity
2020-12-16
In vivo study showed that the CYP3A activity was increased, when morroniside (10, 30 and 90 mg/kg, i.g.) was daily for seven consecutive days. Further, RT-PCR analysis showed that the induction of mRNA T7 High Yield RNA Synthesis by morroniside (10, 30 and 90 mg/kg, i.g.) was 1.13-, 1.43- and 1.79-f
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Previous studies reported that NE and
2020-12-16
Previous studies reported that NE and MHPG are deeply involved in depression and that NE reuptake inhibitors are approved for use in patients with depression (for review, see [2]). We found increased hippocampal content of NE and MHPG in the CORT-treated CRTH2−/− mice (Fig. 3). In the hippocampus, a
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br Conflicts of interest br
2020-12-16
Conflicts of interest Acknowledgements Lung cancer continues to be the leading cause of cancer deaths in the US and worldwide., Non–small-cell lung cancer (NSCLC) remains the predominant form of lung cancer (approximately 85%)., With some improvements in surgical techniques and combined ther
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Introduction Since the recognition of AIDS in more
2020-12-16
Introduction Since the recognition of AIDS in 1981 more than thirty-five years ago, nearly 70 million individuals have been infected with human immunodeficiency virus type 1 (HIV) and roughly half have died (http://www.unaids.org/en/resources/documents/2016/AIDS-by-the-numbers). Although the introd
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Introduction The first reference to
2020-12-16
Introduction The first reference to a possible involvement of orexins in the effects of drugs of abuse appeared in 2003 and showed that orexigenic peptide neurons respond to the chronic administration of morphine followed by abrupt withdrawal symptoms caused by opioid receptor antagonists (Georgesc
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More recently evidence suggests that dysregulation of CRF
2020-12-16
More recently, evidence suggests that dysregulation of CRF signaling may also be implicated in panic disorder. For instance, polymorphisms in the CRF1, but not CRF2, gene have been associated with susceptibility to panic disorder in German and Japanese population samples (Ishitobi et al., 2012, Keck
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TNKS 22 In a previous study we reported that the
2020-12-16
In a previous study we reported that the systemic administration of the α1-adrenergic receptor antagonist prazosin attenuates the deficit in TNKS 22 reward function associated with precipitated nicotine withdrawal (Bruijnzeel et al., 2010). One of the aims of the present experiments was to investig
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