14 research outputs found

    Autoregulatory Mechanisms of Phosphorylation of Checkpoint Kinase 1

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    Recent trends in analytical methods for water-soluble vitamins

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    In this review, recent advances in the analysis of water-soluble vitamins (WSVs) have been reported considering the advantages and disadvantages of various extraction, separation and detection techniques, commonly used for their quantification. Acid hydrolysis, enzyme treatment, SPE based methods and some other extraction methods have been discussed. Particular attention has been devoted to the analytical techniques based on liquid chromatography and electrophoresis. Furthermore, suitability and selectivity of hydrophilic interaction liquid chromatography (HILIC) for WSVs has been discussed in detail. Problems related to these techniques and their possible solutions have also been considered. Special focus has been given to the applications of liquid chromatography (since 2014-2019) for the simultaneous analysis of WSVs and their homologous in complex food samples

    Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma

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    Abstract The Wnt pathway is frequently dysregulated in many cancers, underscoring it as a therapeutic target. Wnt inhibitors have uniformly failed in clinical trials. Here, we report a mechanism of WNT pathway activation through the Semaphorin 3 C neurodevelopmental program in glioma stem-like cells. Sema3C directs ÎČ-catenin nuclear accumulation in a Rac1-dependent process, leading to transactivation of Wnt target genes. Sema3C-driven Wnt signaling occurred despite suppression of Wnt ligand secretion, suggesting that Sema3C drives canonical Wnt signaling independent of Wnt ligand binding. In a mouse model of glioblastoma, combined depletion of Sema3C and ÎČ-catenin partner TCF1 extended animal survival more than single target inhibition alone. In human glioblastoma, Sema3C expression and Wnt pathway activation were highly concordant. Since Sema3C is frequently overexpressed in glioblastoma, Sema3C signaling may be a significant mechanism of resistance to upstream Wnt pathway inhibitors. Dual targeting of Sema3C and Wnt pathways may achieve clinically significant Wnt pathway inhibition

    Tracing historical changes, degradation, and original sources of airborne polycyclic aromatic hydrocarbons (PAHs) in Jilin Province, China, by Abies holophylla and Pinus tabuliformis needle leaves

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    Due to their wide distribution and availability, plant leaves can be considered interesting candidates as biomonitoring substrates for the evaluation of atmospheric pollution. In addition, some species can also retain historical information, for example, related to environmental pollution, due to their leaf class age. In this study, the content of polycyclic aromatic hydrocarbons (PAHs) in Abies holophylla and Pinus tabuliformis needle samples in the function of their class age has been investigated to obtain information regarding the degradation constant for each PAH under investigation (α values ranging from 0.173 to 1.870) and to evaluate the possibility to correlate the presence of PAHs in needles with some important pollution environmental factors. Considering air pollutant variables registered in Jilin Province, interesting correlations (at 95% confidence level) have been found between coal consumption per year and anthracene contents in needles, while fluorene, phenanthrene, and anthracene results correlated with coal consumption. Furthermore, it has been demonstrated that the total PAH concentration in needles, for both species, increased with their age (from 804 to 3604 ng g-1 dry weight), showing a general tendency to accumulate these substances through years. PAH degradation rates increased instead with molecular complexity. This study could be considered a first trial to obtain historical environmental information by pine needles biomonitoring

    Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage

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    Phosphorylation of Chk1 by ataxia telangiectasia-mutated and Rad3-related (ATR) is critical for checkpoint activation upon DNA damage. However, how phosphorylation activates Chk1 remains unclear. Many studies suggest a conformational change model of Chk1 activation in which phosphorylation shifts Chk1 from a closed inactive conformation to an open active conformation during the DNA damage response. However, no structural study has been reported to support this Chk1 activation model. Here we used FRET and bimolecular fluorescence complementary techniques to show that Chk1 indeed maintains a closed conformation in the absence of DNA damage through an intramolecular interaction between a region (residues 31–87) at the N-terminal kinase domain and the distal C terminus. A highly conserved Leu-449 at the C terminus is important for this intramolecular interaction. We further showed that abolishing the intramolecular interaction by a Leu-449 to Arg mutation or inducing ATR-dependent Chk1 phosphorylation by DNA damage disrupts the closed conformation, leading to an open and activated conformation of Chk1. These data provide significant insight into the mechanisms of Chk1 activation during the DNA damage response
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