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cucurbitacin The discoidin domain receptors DDR and DDR
2020-05-26

The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases (RTKs) that are stimulated by collagen in the extracellular matrix (ECM). Unlike most other RTKs, they form ligand-independent stable dimers that are non-covalently linked. This ECM activation induces receptor phosphorylati
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br Discussion Nowadays data of uncommon
2020-05-26

Discussion Nowadays, data of uncommon EGFR mutations are limited, considering that patients carrying these rare alterations are usually excluded from clinical trials. Available survival data of activity of EGFR TKIs on this class of mutations, coming from a small number of usually retrospective s
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br Multi subunit RINGs There are RING type
2020-05-26

Multi-subunit RINGs There are RING-type E3s that exist as multi-subunit assemblies (see Fig. 3B). A striking example is the Cullin RING Ligase (CRL) superfamily [35], which exhibits enormous plasticity in substrate specificity. Each CRL subfamily is characterized by a cullin protein (Cul-1, 2, 3,
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Then what is the solution to tackle DNA
2020-05-26

Then what is the solution to tackle DNA damage-induced metabolic decline? The culprit here may be not DNA damage signaling per se, but rather the persistent activation of the DNA damage signaling pathways due to age-related accumulation of DNA damage. DNA repair, including repair by NHEJ, is an esse
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Introduction Maintenance of genome integrity is essential
2020-05-26

Introduction Maintenance of genome integrity is essential for life, and faithful DNA replication and repair ensure this. One of the most important parameters for DNA maintenance is the regulation of optimal concentrations of the four 5′-deoxyribonucleoside-triphosphates (dNTPs) the precursors for D
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Given the structural similarity of BMAA to other amino
2020-05-26

Given the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a previously unrecognised mechanism for BMAA action. Materials and methods Results and discussion We first examined whether chemical
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br Introduction Malaria remains a serious parasitic disease
2020-05-26

Introduction Malaria remains a serious parasitic disease in tropical areas due to its high morbidity and mortality rates. It is estimated that 212 million cases occurred globally in 2015, leading to 429, 000 deaths, most of which were in children aged under 5 years in Africa [1,2]. The protozoans
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The molecular formula of was assigned as C
2020-05-26

The molecular formula of 2 was assigned as C12H12N2O2 by the positive HRESIMS at m/z 217.0973 [M+H]+ (calcd for 217.0972), 13C NMR and DEPT spectra, having 8 degrees of unsaturation. The 1H NMR spectrum contains an ABX spin system comprised of resonances at δH 7.47 (d, J=1.9Hz, H-2′), 6.86 (d, J=8.3
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Introduction Cytochrome P CYP A is the most important enzyme
2020-05-26

Introduction Cytochrome P450 (CYP)3A is the most important enzyme involved in the metabolism of 30–40% of currently prescribed drugs [1]. The Ramipril level and activity of CYP3A show large intra- and inter-individual variability, which contributes to unpredictable drug response and toxicity. A mu
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With a favorable spectrum of CRTh dependent
2020-05-26

With a favorable spectrum of CRTh2 dependent in vitro and in vivo efficacy demonstrated, the off-target activity of compound 18 was investigated, first against a panel of prostanoid receptors and related eicosanoid targets (Table 8), where no significant activities at 10μM concentration were found i
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Regarding the mechanism of action
2020-05-26

Regarding the mechanism of action of CRF, several studies have shown that low doses of CRF may preferentially activate CRF1 receptors in glutamatergic projection neurons, serotoninergic neurons or glutamatergic collaterals in the medial prefrontal cortex (Vertes, 2004). Indeed, prosencephalic inacti
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The genetic asymmetries between parental genomes are also th
2020-05-26

The genetic asymmetries between parental genomes are also the subject of genetic conflict theory. This concept proposes that paternally inherited imprinted genes “extract” nutrients from the mother during gestation. By contrast, maternally inherited genes counteract the effect of paternal genes (Con
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The Penicillium strain used in
2020-05-26

The Penicillium strain used in this work was isolated from Atlantic forest soil and previously screened as lipase producer (Tauk-Tornisielo et al., 2005). The immobilization was previously evaluated using hydrophobic supports, i.e. agarose based butyl-(But), phenyl-(Phe) and octyl-Sepharose (Oct), a
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Most remarkably an essentially identical collagen binding
2020-05-25

Most remarkably, an essentially identical collagen-binding mode to DDR2 is employed by SPARC, an α-helical matricellular protein unrelated to DDR2 that also recognizes the GVMGFO motif in collagen (Giudici et al., 2008, Hohenester et al., 2008). The convergence of binding mechanisms suggests that th
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br Cytokines potent mediators of ILC function The different
2020-05-25

Cytokines – potent mediators of ILC function The different ILC players are portrayed in three categories, ILC1, ILC2 and ILC3, based on the cytokines they produce and transcription factors (TFs) that guide their differentiation [8] (Figure 1). Cytokines are the most extensively studied stimuli fo
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