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We did not observe inhibition of vCPH by
2019-10-21
We did not observe inhibition of vCPH by any of the TCA cycle intermediates (apart from the metal chelators citrate and isocitrate), nor by the factor inhibiting HIF (FIH; a 2OG-dependent asparaginyl hydroxylase) inhibitor N-oxalyl d-phenylalanine (NOF) or the γ-butyrobetaine dioxygenase inhibitor m
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Although intact Chk is distributed throughout
2019-10-21
Although intact Chk is distributed throughout the nucleus and the cytoplasm (Fig. 1), the deletion of the SH2 domain greatly augments nuclear localization of Chk. The SH2 domain-deleted mutants might lose the ability to localize to the exterior of the nucleus due to a lack of the binding to a hypoth
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br Introduction Our understanding of how ligands
2019-10-21
Introduction Our understanding of how ligands interact with G protein coupled receptors is evolving, particularly the recognition that some have the ability to preferentially activate a subset of intracellular signalling cascades – so called pathway biased ligands [1]. Additionally, it is now acc
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Developmental relationships between CD bright
2019-10-21
Developmental relationships between CD56bright and CD56dim NK gallic acid synthesis remain unresolved; however, several studies indicate that the former is a precursor of the latter. An NK subset with intermediate features between CD56bright and CD56dim has been identified, corroborating this devel
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Interestingly all three lesions that significantly inhibited
2019-10-21
Interestingly, all three lesions that significantly inhibited transcription – CPD, εA and the AP site, – promoted insertion of WZ3146 sale residues opposite the damaged nucleotide. Thus, bacterial RNAP seems to follow the so-called ‘A-rule’ for incorporation of nucleotides opposite AP-sites and bul
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Previous studies found that depression primarily
2019-10-19
Previous studies found that depression primarily results from impaired monoaminergic neurotransmission systems [1], [2]. The glutamatergic and GABAergic systems as well as several neuropeptide systems have also been the focus of pathophysiological studies on depression [1], [2]. Inflammatory cytokin
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The large body of structural knowledge that is currently
2019-10-19
The large body of structural knowledge that is currently available for CRM1 has contributed to atomic level and mechanistic understanding of many steps in the CRM1 nuclear export cycle. However, structural analysis could still inform on several outstanding questions and guide future discoveries pert
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SB 204990 br Results br Discussion Adaptive drug resistance
2019-10-19
Results Discussion Adaptive drug resistance is a major challenge to the clinical success of cancer therapies. Incomplete inhibition of oncogenic signaling allows survival of “drug-tolerant” tumor cells, which persist in that state for variable periods before acquiring additional genetic mutati
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Among the Ub interactions observed in the HOIP
2019-10-19
Among the ~Ub interactions observed in the HOIP structure is one that involves a RING2 domain (from the non-cognate HOIP) [47]. A similar binding interaction was defined between HHARI RING2 and the hydrophobic patch on Ub by NMR [54]. HHARI RING2 mutations that ablate the interaction inhibit formati
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Apremilast Models and theories The CPA equation of state is
2019-10-18
Models and theories The CPA equation of state is composed predominantly of two parts: physical item and the association item based on the thermodynamic perturbation theory [21], [22], [26], [27]. The physical item is used to represent intermolecular physical interaction, usually representing the SR
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Furan analogs and N methylpyrrole analogs had completely
2019-10-18
Furan analogs and N-methylpyrrole analogs had completely different SARs. For example, replacement of the furan-2-sulfonyl moiety of 6 with the furan-3-sulfonyl moiety resulted in 8 with a decreased EP1 salidroside mass affinity and an increased antagonist activity, while the corresponding chemical
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br Discussion The regulation of intracellular cholesterol le
2019-10-17
Discussion The regulation of intracellular cholesterol levels is a biological process of vital importance for cellular function and integrity, and involves robust transcriptional and post-transcriptional mechanisms that are sensitive to metabolic feedback control. Amongst post-transcriptional mec
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br Introduction As a strong analgesic morphine is often
2019-10-17
Introduction As a strong analgesic, morphine is often used to treat acute and chronic pain. However, morphine is a substance with low lipid solubility that slowly enters the nerve tissue through the blood–brain barrier and produces neurotoxicity. Morphine-induced neurotoxicity can be produced aft
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ATRX belongs to the switch sucrose
2019-10-17
ATRX belongs to the switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression (Gibbons et al., 1995). Most of these mutations are located in two highly conserved regions of the ATRX protein: a
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The unique property of mutant IDH in producing an
2019-10-17
The unique property of mutant IDH1/2 in producing an oncometabolite that has no known physiological function makes mutant IDH enzymes as obvious potential therapeutic targets for the treatment of IDH-mutated tumors (Rohle et al., 2013, Wang et al., 2013). Clinical studies have also suggested the pre
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