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The second patient had a
2022-01-12
The second patient had a homozygous substitution within exon 6 (c.538C>T). The parents were heterozygous and showed no clinical or immunological defect. The mutation has been predicted to alter a potential exonic splicing enhancer (ESE) site. Therefore, exon 6 skipping could be explained by the ESE-
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In first wave first generation drugs telaprevir
2022-01-12
In 2013, first-wave, first-generation drugs telaprevir and boceprevir was the first protease inhibitors (PIs) incorporated in Brazilian Clinical Guidelines for the treatment of patients infected with HCV Anhydrotetracycline hydrochloride 1. Based on this 2013 Clinical Guideline, telaprevir could be
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A more quantitative view of
2022-01-12
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 or
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The fibulins are a newly abundantly in the basement membrane
2022-01-12
The fibulins are a newly abundantly in the basement membrane of blood vessels. Among them, fibulin-1 is essential for elastin polymerization. Tropoelastin cannot be assembled into mature elastin fibrils without the functional fibulin-1. In adult blood vessels, pronounced fibulin 1 deposition can be
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br Materials and methods br Results br Discussion Early
2022-01-12
Materials and methods Results Discussion Early studies in the mid 1980s tentatively identified cCMP in tissues using fast atom bombardment MS [3], [4], but specificity and sensitivity of the method are insufficient for unequivocal identification as compared to modern MS analytical methods.
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All experiments in this study were performed at pD
2022-01-12
All experiments in this study were performed at pD 6.1 for reasons described above. This leaves a question about the implications of stereochemistry in vivo. At physiological pH the GSTP1-1 catalyzed rate of EASG formation is only 1.1-fold higher than the non-enzymatic rate [26]. However, when human
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Having identified initial leads and further lead optimizatio
2022-01-12
Having identified initial leads and (), further lead optimization was initiated on B- and C-rings to afford compounds with improved potency. Initial set of substituted imidazole-biphenyl-carboxylic cyclin dependent kinases derivatives – and () were evaluated for GSNOR potency. Among this, fluoro
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Third we performed correlation analysis between the results
2022-01-12
Third, we performed correlation analysis between the results obtained using DMR agonist assay in HT-29 and Tango assay in the engineered U2OS cells. First, we compared their relative efficacy, the maximal responses after normalized to the maximal responses of zaprinast obtained using both DMR and Ta
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Long non coding RNAs lncRNAs are mRNA
2022-01-11
Long non-coding RNAs (lncRNAs) are mRNA-like transcripts of greater than 200 nucleotides (nt), with little or no protein-coding potential [13,14]. LncRNAs have been suggested to participate in transcription and post-transcription regulation as scaffolds, guides, decoys or repressors, activators, and
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To identify inhibitors of the Hh GLI signaling pathway
2022-01-11
To identify inhibitors of the Hh/GLI signaling pathway from natural resources, we have recently reported the successful construction of a cell-based screening assay system for the Hh/GLI signaling pathway (Fig. 1). This is an assay using a GLI-dependent luciferase reporter in human keratinocyte cell
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Ghrelin is mostly known for its
2022-01-11
Ghrelin is mostly known for its orexigenic properties, whereas the role of DAG on feeding is controversial with studies claiming an orexigenic, anorexigenic or no effect (Inhoff et al, 2009, Toshinai et al, 2006). One of these studies was that of Toshinai and colleagues, who found a link between the
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So far several methods have been used
2022-01-11
So far, several methods have been used to monitor the level of GJC and its regulation in astrocytes studied in acute Vanoxerine receptor slices (see Giaume et al., 2012). This mainly includes approaches based either on electrophysiological properties of gap junction channels or on “dye coupling” exp
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In single channel studies Zn
2022-01-11
In single channel studies, Zn2+ primarily inhibits GABA-A receptors through the reduction of channel opening probability (Smart, 1992, Smart et al., 1994). In slice recordings, Zn2+ significantly reduces phasic mIPSC event amplitude and kinetics, as well as desensitization kinetics (Barberis et al.,
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It should be noted that the applied steered unfolding
2022-01-11
It should be noted that the applied steered unfolding of the i-motif and G-quadruplex satisfies the conditions of Jarzynski inequality for computations of the free energy change. [41] However, in order to reproduce the free energy with an adequate quality a number of nonequilibrium unfolding transi
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In a follow up study the same
2022-01-11
In a follow up study, the same research group further characterized FFA4 involvement in DU145 and PC-3 cancer cell lines by demonstrating that the anti-proliferative and anti-migration activities of FFA4 require the presence of LPA1 receptor (LPA1R), suggesting a mechanism consistent with negative c
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