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Despite the association with asthma it is not surprising
2021-12-29
Despite the association with asthma, it is not surprising that we did not find a relation between the percent predicted FEV1 and SNPs in GSNOR. FEV1 measured on a routine clinic visit is likely to be normal in most asthmatic children. FEV1 in children reflects a complex mix of factors in the growth
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Selective pharmacological inhibition of tonic currents indic
2021-12-29
Selective pharmacological inhibition of tonic currents indicated that the effects of gp120 are predominantly mediated by α5-containing GABAARs. The other dominant subtype that contributes to tonic current in the hippocampus, the δ-containing GABAAR, was unaffected by gp120 treatment. Additionally, i
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Generally speaking the regulation of GnIH on gonadotropins s
2021-12-29
Generally speaking, the regulation of GnIH on gonadotropins synthesis and release, although controversial, could be direct and/or indirect via GnRH, among others peptides. In this sense, different scenarios have been reported in vertebrates. In mammalian and avian species, GnIH fibers reach the med
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In silico analysis revealed structural
2021-12-29
In silico analysis revealed structural similarities between the CpMutY and the EcMutY which share typical domains and structural motifs (Fig. 5), common to a wide range of structurally related DNA repair enzymes. These include an endonuclease III domain, involved in excision of damaged pyrimidines,
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br Conclusions and future perspectives br Declarations of in
2021-12-28
Conclusions and future perspectives Declarations of interest Acknowledgements The authors thank Mrs. Kamala Pandey for the help in the preparation of this manuscript. This work was supported by NIH grants R01HL057531 and R01HL062147. Introduction Separation of short exons by long non-co
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Since TgGC resisted several knockout attempts with CRISPR Ca
2021-12-28
Since TgGC resisted several knockout attempts with CRISPR-Cas9, we utilized traditional epitope tagging and an auxin-inducible degron (AID) system (Brown et al., 2017, Brown et al., 2018, Long et al., 2017) to detect and regulate TgGC expression. TgGC localizes to the apical cap region of the plasma
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Because of its excellent GPR potency good hERG selectivity
2021-12-28
Because of its excellent GPR119 potency, good hERG selectivity and favorable rat t, Butyrolactone 3 synthesis was scaled-up and further profiled. The synthetic protocols described in , were both suitable for a multi-gram scale synthesis of compound . An off-target screen was performed against an ext
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Curcumin is the active ingredient extracted from the natural
2021-12-28
Curcumin is the active ingredient extracted from the natural medicine turmeric rhizome (Goel et al., 2008, Aggarwal and Harikumar, 2009). Studies have shown that curcumin has anti-tumor, anti-inflammatory, antioxidant and antimicrobial properties (Larsen et al., 2007, López-Lázaro, 2008). Although c
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In addition to inactivation of Notch
2021-12-27
In addition to inactivation of Notch, we found that the combination of BTZ and GSI-I downregulated ERK phosphorylation in ALK+ ALCL cells, and we speculate this may occur through the inhibition of upstream regulators of the ERK pathway. These findings emphasize the functional complementation of the
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Optimization of the tetrahydroindazole series led
2021-12-27
Optimization of the tetrahydroindazole series led to the discovery of two moderately potent γ-secretase modulators, 2-cyclobutane and 2-hydroxy-2-methylpropane which were subsequently evaluated in a kinetic aqueous solubility assay. Unfortunately, neither analog demonstrated improved solubility ().
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br Results and discussion br Conclusion In the continued
2021-12-27
Results and discussion Conclusion In the continued SAR study of our previous heterocycle scaffolds represented by Sorbitol 2, we focused especially on improving their drug-like physicochemical properties directed by lipophilicity, LE and LLE. After explored several heterocyclic scaffolds, the
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br FGF FGFR pathway as predictive factor Several
2021-12-27
FGF/FGFR pathway as predictive factor Several studies have identified FGFR1 amplification as the major predictive factor of response to FGFR inhibitors [26], [27]. However, in a recent study on lung cancer cell lines with ponatinib, FGFR1 mRNA and protein expression, together with FGF2 and FGF9 m
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Regulation of gene expression in mammalian cells is
2021-12-27
Regulation of gene expression in mammalian cells is governed by the epigenetic machinery, which includes several distinctive yet entangled branches. DNA and histone modifying enzymes, non-coding regulatory RNAs, and ATPase-dependent chromatin remodeling proteins all contribute to the dynamic alterat
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br Material and methods br Results br Discussion In vitro
2021-12-27
Material and methods Results Discussion In vitro testing is necessary to study DAA activity and putative RASs. Compared to enzymatic assays and replicons, HCV infectious culture systems reflect the full viral life cycle and previous results in these systems reflected clinical data.[13], [14
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A more quantitative view of kinase specificity suggests
2021-12-27
A more quantitative view of kinase specificity suggests a continuum of phosphorylation rates for the various substrates of a particular kinase (Figure 4A). Such differences in ‘substrate quality’ can arise from variations in phosphorylation site or docking sequences and may explain why the timing o
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