RAS mutations occur frequently in human cancer and activated RAS signalling contributes to tumour development and progression. Apart from its oncogenic effects on cell growth, active RAS has ...tumour-suppressive functions via its ability to induce cellular senescence and apoptosis. RAS is known to induce p53-dependent cell cycle arrest, yet its effect on p53-dependent apoptosis remains unclear. We report here that apoptosis-stimulating protein of p53 (ASPP) 1 and 2, two activators of p53, preferentially bind active RAS via their N-terminal RAS-association domains (RAD). Additionally, ASPP2 colocalises with and contributes to RAS cellular membrane localisation and potentiates RAS signalling. In cancer cells, ASPP1 and ASPP2 cooperate with oncogenic RAS to enhance the transcription and apoptotic function of p53. Thus, loss of ASPP1 and ASPP2 in human cancer cells may contribute to the full transforming property of RAS oncogene.
The view that successful memory performance depends importantly on the extent to which there is a match between the encoding and retrieval conditions is commonplace in memory research. However, ...Nairne (
Memory
,
10
, 389–395,
2002
) proposed that this idea about trace–cue compatibility being the driving force behind memory retention is a myth, because one cannot make unequivocal predictions about performance by appealing to the encoding–retrieval match. What matters instead is the relative diagnostic value of the match, and not the absolute match. Three experiments were carried out in which participants memorised word pairs and tried to recall target words when given retrieval cues. The diagnostic value of the cue was varied by manipulating the extent to which the cues subsumed other memorised words and the level of the encoding–retrieval match. The results supported Nairne’s (
Memory
,
10
, 389–395,
2002
) assertion that the diagnostic value of retrieval cues is a better predictor of memory performance than the absolute encoding–retrieval match.
Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast ...imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73–94 years, of whom 204 pairs experienced the death of one or both co-twins during 9–10 years of follow-up (1997–2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL50) and shortest 25% (mTRFL25) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL50: 0.59, 95% CI: 0.52, 0.66; mTRFL25: 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3–4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span.
In this work, three different states (as-cast, homogenized and ECAP processed) of Mg98.5Y1Zn0.5 alloys with high theoretical hydrogen storage capacity (7.2 wt%) were prepared and comminuted into ...chips by filing. Then their hydrogen storage properties and underlying mechanisms were systematically investigated through experimental and first-principles calculations approaches. The results show that the activation properties of these alloys are enhanced in the order of homogenized, as-cast and ECAP processed states, which is closely associated with the size of filed chips. After activation, the as-cast and ECAP processed samples exhibit the superior hydrogen adsorption/desorption kinetics compared with the homogenized one. Interestingly, the as-cast sample presents the similar or even better kinetics relative to the ECAP processed one. This should be attributed to the more uniform dispersion of in-situ formed YH2 nanohydride in the as-cast alloy, which remarkably boosts the reversible hydrogen storage properties of Mg matrix by the synergistic pinning and catalytic effects. First-principles calculations reveal that the doping of Y not only reduces the activation energy of H2 dissociation on Mg surface, but also decreases the hydrogen removal energy of H atom from MgH2 bulk, which accounts well for the excellent hydrogen sorption kinetics of Mg98.5Y1Zn0.5 alloys.
•Hydrogen storage properties of different states of Mg98.5Y1Zn0.5 alloys are studied.•As-cast and ECAP samples exhibit superior kinetics relative to homogenized one.•As-cast sample presents similar or better kinetics relative to ECAP processed one.•In-situ formed YH2 nanohydride plays pinning and catalytic effects on Mg matrix.•Hydrogen storage mechanisms of Mg98.5Y1Zn0.5 are revealed based on DFT calculations.
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▶ The composite catalysts Co-ZSM-5(L) are prepared by a simple route. ▶ Co-ZSM-5(L) exhibits a high activity for the epoxidation of alkenes with air. ▶ These solids are highly ...reusable heterogeneous catalysts. ▶ Based on the experiments, one possible reaction mechanism is proposed.
Three tridentate or bidentate Schiff-base ligands inclusive of salicylaldehyde benzoylhydrazone (L1), vanillic aldehyde benzoylhydrazone (L2) and 4-methyl benzaldehyde benzoylhydrazone (L3), have been designed, synthesized and employed to coordinate with Co2+ ions and ion-exchanged Co-ZSM-5 forming several Co-L complexes and Co-ZSM-5(L) composite catalysts. The catalytic epoxidation of several alkenes with dry air has been carried out at 90°C under atmospheric pressure using Co-L complexes and Co-ZSM-5(L) catalysts (using TBHP in small amounts as the initiator). In contrast, the catalysts Co-ZSM-5(L) shows higher catalytic activity than Co-ZSM-5 itself and Co-L complexes. Among three Co-ZSM-5(L) catalysts, Co-ZSM-5(L1) exhibits the highest activity for the selective epoxidation of alkenes. Recycling studies show the recyclability of Co-ZSM-5(L1) as a heterogeneous catalyst, which does not lose the catalytic activity after even eight reuses appreciably. Based on the experiments, one possible reaction mechanism is proposed.
Background The role of microRNAs (miRNAs), a key class of regulators of mRNA expression and translation, in patients with eosinophilic esophagitis (EoE) has not been explored. Objective We aimed to ...identify miRNAs dysregulated in patients with EoE and assess the potential of these miRNAs as disease biomarkers. Methods Esophageal miRNA expression was profiled in patients with active EoE and those with glucocorticoid-induced disease remission. Expression profiles were compared with those of healthy control subjects and patients with chronic (noneosinophilic) esophagitis. Expression levels of the top differentially expressed miRNAs from the plasma of patients with active EoE and patients with EoE remission were compared with those of healthy control subjects. Results EoE was associated with 32 differentially regulated miRNAs and was distinguished from noneosinophilic forms of esophagitis. The expression levels of the most upregulated miRNAs (miR-21 and miR-223) and the most downregulated miRNA (miR-375) strongly correlated with esophageal eosinophil levels. Bioinformatic analysis predicted interplay of miR-21 and miR-223 with key roles in the polarization of adaptive immunity and regulation of eosinophilia, and indeed, these miRNAs correlated with key elements of the EoE transcriptome. The differentially expressed miRNAs were largely reversible in patients who responded to glucocorticoid treatment. EoE remission induced a single miRNA (miR-675) likely to be involved in DNA methylation. Plasma analysis of the most upregulated esophageal miRNAs identified miR-146a, miR-146b, and miR-223 as the most differentially expressed miRNAs in the plasma. Conclusions We have identified a marked dysregulated expression of a select group of miRNAs in patients with EoE and defined their reversibility with glucocorticoid treatment and their potential value as invasive and noninvasive biomarkers.
Carbon nanotube (CNT) sponge exhibits unique porous and hierarchical structure that are beneficial to the design of ultralight and tough composites. In this study, CNT sponges (undoped and boron ...doped) reinforced polydimethylsiloxane (PDMS) composites were fabricated. Mechanical properties of the composite, including compressive modulus, rate-dependent modulus, stress relaxation behaviors, dynamic viscoelastic properties, and their dependency on temperature, were systematically investigated. A micromechanical model, Mori-Tanaka model, was validated to describe the mechanical behaviors of CNT sponge reinforced composites. By coupling with boron-doped CNT sponge, PDMS composites showed remarkable improvement of mechanical properties, including compressive modulus (70%), viscous modulus (243%) and damping capacity (50%). Such reinforcement effects can be controlled by the morphology of CNT sponges, as the boron-doped and undoped nanocomposites showed distinct viscoelastic behaviors. The results proved that CNT sponge reinforcement is a promising strategy to develop engineering composites with both outstanding mechanical stiffness and controllable viscoelastic performances.
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•Nano-composites are fabricated and characterized using PDMS and 3D CNT sponge or boron-doped CNT sponge.•Mechanical strength and viscoelastic behaviors of the new composites are improved significantly by the 3D CNT sponges.•CNT composites show 70% increase in elastic modulus, 243% increase in viscous modulus in comparison to the pure PDMS.•Mechanical properties of the new composites are highly dependent on the 3D structure of CNTs.•The new nano-composite can advance the design of engineering materials that require outstanding viscoelastic behaviors.
Effects of various spatial scales of water table dynamics on land–atmospheric methane (CH4) exchanges have not yet been assessed for large regions. Here we used a coupled hydrology–biogeochemistry ...model to quantify daily CH4 exchanges over the pan-Arctic from 1993 to 2004 at two spatial scales of 100 km and 5 km. The effects of sub-grid spatial variability of the water table depth (WTD) on CH4 emissions were examined with a TOPMODEL-based parameterization scheme for the northern high latitudes. We found that both WTD and CH4 emissions are better simulated at a 5 km spatial resolution. By considering the spatial heterogeneity of WTD, net regional CH4 emissions at a 5 km resolution are 38.1–55.4 Tg CH4 yr−1 from 1993 to 2004, which are on average 42% larger than those simulated at a 100 km resolution using a grid-cell-mean WTD scheme. The difference in annual CH4 emissions is attributed to the increased emitting area and enhanced flux density with finer resolution for WTD. Further, the inclusion of sub-grid WTD spatial heterogeneity also influences the inter-annual variability of CH4 emissions. Soil temperature plays an important role in the 100 km estimates, while the 5 km estimates are mainly influenced by WTD. This study suggests that previous macro-scale biogeochemical models using a grid-cell-mean WTD scheme might have underestimated the regional CH4 emissions. The spatial scale-dependent effects of WTD should be considered in future quantification of regional CH4 emissions.
Src family tyrosine kinases (SFKs) play key roles in regulating signal transduction in cellular processes. However, hyper-activated SFKs lead to uncontrolled cell proliferation and cancers. For both ...Src SH2 and SH3 domains involve in the regulation of tumorigenesis signal pathways, the SH2 and SH3 inhibition strategies are expected to block the protein-protein interactions between SFKs and their corporation proteins to abolish the signal transduction. Many inhibitors of SH2 and SH3 domain have been identified. Herein, some predominant examples of these inhibitors are reviewed.
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