63 research outputs found

    Additional file 1: of Quantitative framework for ordered degradation of APC/C substrates

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    Supplementary Figures. Figure S1. Ordered degradation of APC/C substrates. Figure S2. Determination of the time of degradation onset. Figure S3. Mechanisms that determine substrate degradation timing all change degradation onset. Figure S4. Ordinary differential equations for analysis of substrate degradation in the one-substrate model. Figure S5. APC/CCdc20 levels in the cell are lower than those of its substrates. Figure S6. Including deubiquitination in the model further limits the parameter space that generates a good delay in degradation onset and a fast rate of degradation. Figure S7. Changing k d influences T95 when not all APC/CCdc20 is bound to the substrate. Figure S8. Effects of doubling the concentration of C on T95 of S. (PDF 5283 kb

    From Starting Formation to the Saturation Content of the β‑Phase in Poly(9,9-dioctylfluorene) Toluene Solutions

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    In this research, the relationship between chain aggregation and poly­(9,9-dioctylfluorene) (PFO) β-phase content with a change of the PFO solution concentration is investigated. Photoluminescence and UV–vis absorption spectra are used to explore the PFO β-phase and its content. Chain aggregation is explored by dynamic light scattering (DLS). It is found that the chain aggregation size of the starting to form PFO β-phase is approximately 100 nm. The β-phase content increases with the chain aggregation degree. When the β-phase content is in the range of 44% ± 2%, the maximum value of the content (saturation content) of the β-phase is reached and cannot be changed by any external field that could induce β-phase formation. Therefore, the concept of the saturation content of the PFO β-phase is first proposed. The mechanism from PFO β-phase formation to saturation content is explored by DLS and atomic force microscopy. This research is significant to understand and control the molecular chain condensed-state process as well as phase transition from solution to film to achieve a photoelectric device with high charge carrier mobility, stability, and efficiency

    Binding selectivity-dependent molecular mechanism of inhibitors towards CDK2 and CDK6 investigated by multiple short molecular dynamics and free energy landscapes

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    Understanding selectivity-dependent molecular mechanism of inhibitors towards CDK2 over CDK6 is prominent for improving drug design towards the CDK family. Multiple short molecular dynamics (MD) simulations combined with MM-GBSA approach are adopted to investigate molecular mechanism on binding selectivity of inhibitors X64, X3A, and 4 AU to CDK2 and CDK6. The RMSF analysis and calculations of molecular surface areas indicate that local structural and global flexibility of CDK6 are stronger than that of CDK2. Based on dynamics cross-correlation maps (DCCMs), motion modes of CDK2 and CDK6 produce difference due to associations of X64, X3A, and 4 AU. The calculated binding free energies (BFEs) demonstrate that the compensation between binding enthalpy and entropy of X64, X34, and 4 AU is a key force driving selectivity of inhibitors towards CDK2 over CDK6. This work provides valuable information for designing highly selective inhibitors towards CDK2 and CDK6 and further promotes identification of efficient anticancer drugs in the future.</p

    Two new ceramides from the fruit pulp of <i>Acanthopanax senticosus</i> (Rupr. et Maxim) Harms

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    <div><p>Two new ceramides, (3<i>S</i>,4<i>S</i>,5<i>R</i>)-3-octadecanoylamino-4-hydroxy-5-dodecane-2,3,4,5-tetrahydrofuran (<b>1</b>) and (3<i>S</i>,4<i>S</i>,5<i>R</i>)-3-[(2<i>R</i>)-2-hydroxyhexacosanoylamino]-4-hydroxy-5-[(4<i>E</i>)-dodecane-4-ene]-2,3,4,5-tetrahydrofuran (<b>2</b>), together with eight known compounds, eleutheroside A (<b>3</b>), eleutheroside B (<b>4</b>), eleutheroside E (<b>5</b>), 7-hydroxy-6-methoxy-coumarin (<b>6</b>), 6,7-dimethoxycoumarin (<b>7</b>), 5α,8α-epidioxyergosta-6,22-dien-3-ol (<b>8</b>), stigmasterol (<b>9</b>) and rutin (<b>10</b>), were isolated from the fruit pulp of <i>Acanthopanax senticosus</i> (Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D NMR and MS).</p></div

    Study of β phase and Chains Aggregation Degrees in Poly(9,9-dioctylfluorene) (PFO) Solution

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    In this work, the effects of solvation and desolvation on the β phase of poly­(9,9-dioctylfluorene) (PFO) are studied. The content of β phase is approximately calculated for comparison. The content of β phase can be enhanced up to 40% by the solvation effect and become a metastable state; the desolvation effect is a dynamic process and can enhance the content of β phase remarkably by 18%age units. It is found that the contents of β phase are always changing with the aggregation degrees of PFO chains. To fully understand it, the concepts of mesoscopic aggregates and macroscopic aggregates are proposed and well proved by the filtration experiment. In the solution (the ethanol content less than 30%), the mesoscopic aggregates are beneficial to enhance the content of β phase; in the solution (the ethanol content more than 40%), which is close to the condensed state of fabricated optoelectronic film, the macroscopic aggregates can make the content of β phase not only much higher but also stable. The content of β phase can be controlled by changing the aggregation characteristics of PFO chains in solution. This work will be significant in fabricating the optoelectronic devices from solutions to films with high carrier mobility and good stability

    Study of the α‑Conformation of the Conjugated Polymer Poly(9,9-dioctylfluorene) in Dilute Solution

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    In this work, the α-conformation (individual locally separated chain) of the conjugated polymer poly­(9,9-dioctylfluorene) (PFO) in dilute solution is studied by the following three points: the Mark–Houwink exponent <i>a</i>, the fractal dimension <i>D</i>, and the form factor <i>R</i><sub>g</sub>/<i>R</i><sub>h</sub>. From the result of <i>a</i>, the α-conformation of PFO is considered to have a semirigid chain conformation in dilute solution. We establish the mathematical relationship between the Mark–Houwink exponent <i>a</i> and the fractal dimension <i>D</i> in dilute solution. To prove the rationality of this mathematical relationship, the classic polymer polystyrene (PS) is used for comparison. According to the result of <i>D</i>, it can be known that the α-conformation of PFO has a relatively loose and extended chain conformation. Moreover, we use light scattering to get the form factor <i>R</i><sub>g</sub>/<i>R</i><sub>h</sub> of the PFO solution in which the α-conformation and β-conformation coexist. It is found that <i>R</i><sub>g</sub>/<i>R</i><sub>h</sub> increases with the proportion of α-conformation, which indicates that the α-conformation of PFO has a loose and extended chain conformation, and this result agrees well with the conclusions drawn from <i>a</i> and <i>D</i>. On the basis of the fact that the β-conformation (ordered conformation) and α-conformation of PFO can transform into each other in solution, this work is significant for the control of the β-conformation and will have a potential meaning to increase the charge carrier mobility and efficiency from the PFO solution to films

    Effect of chromium (VI) on the multiple nitrogen removal pathways and microbial community of aerobic granular sludge

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    <p>The frequent appearance of Cr(VI) significantly impacts the microbial metabolism in wastewater. In this study, long-term effects of Cr(VI) on microbial community, nitrogen removal pathways and mechanism of aerobic granular sludge (AGS) were investigated. AGS had strong resistance ability to 1.0 mg/L Cr(VI). 3.0 mg/L Cr(VI) increased the heterotrophic-specific ammonia uptake rate (HSAUR) and heterotrophic-specific nitrate uptake rate (HSNUR) transiently, whereas 5.0 mg/L Cr(VI) sharply decreased the specific ammonia uptake rate (SAUR), specific nitrate uptake rate (SNUR) and simultaneous nitrification denitrification rate (SNDR). It was found that Cr (VI) has a greater inhibitory effect on autotrophic nitrification (ASAUR), and the maximal inhibition rate (IR) was 139.19%. Besides, the inhibition of Cr (VI) on nitrogen removal process belongs to non-competitive inhibition. Cr(VI) had a weaker negative impact on heterotrophic bacteria compared with that on autotrophic bacteria. Denaturing gradient gel electrophoresis analyses suggest that <i>Acidovorax</i> sp., <i>flavobacterium</i> sp., <i>uncultured soil bacterium</i>, <i>uncultured nitrosospira</i> sp., <i>uncultured prokaryote</i>, <i>uncultured β-proteobacterium</i> and <i>uncultured pseudomonas</i> sp. were the dominant species. The inhibition of Cr(VI) on nitrite-oxidizing bacteria was the strongest, followed by ammonia-oxidizing bacteria and denitrifying bacteria. Linear correlations between bacterial count and biomass-specific uptake rate were observed when the Cr(VI) concentration exceeded 3 mg/L. This study revealed the effect of Cr(VI) on nitrification is more serious than that on denitrification. Autotrophic and heterotrophic nitrification, heterotrophic denitrification and simultaneous nitrification denitrification played a significant role on nitrogen removal under Cr(VI) stress.</p

    Heparin-Binding EGF-Like Growth Factor Induces Heart Interstitial Fibrosis via an Akt/mTor/p70s6k Pathway

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    <div><p>Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is essential for maintaining normal function of the adult heart and is known to play an important role in myocardial remodeling. In the present study, we observed that heart-specific HB-EGF transgenic (TG) mice had systolic dysfunction with decreased fractional shortening (FS%), increased end-systolic diameter (LVIDs) at 5 months of age, increased heart fibrosis, and increased mRNA expression of Col1α1 and Col3α1 at 1, 3, 5 and 7 months of age compared to nontransgenic (NTG) littermates. However, the left ventricular anterior wall thickness at end-systole (LVAWs) of the TG mice was not different than the NTG mice. Phosphorylation levels of Akt, mTor and p70s6k were increased due to HB-EGF expression in TG mice compared with the NTG mice at 3 and 7 months of age. Additionally, activated Akt, mTor and p70s6k were co-localized with vimentin to cardiac fibroblasts isolated from TG mice. Furthermore, HB-EGF significantly increased phosphorylation levels of Akt, mTor and p70s6k and increased expression of type I collagen in cultured primary cardiac fibroblasts. Rapamycin (Rapa) and CRM197, inhibitors of mTor and HB-EGF respectively, could inhibit the expression of type I collagen in the cultured primary cardiac fibroblasts and Rapa suppressed interstitial fibrosis of the heart tissues <em>in vivo</em>. In addition, a BrdU assay showed that HB-EGF increased proliferation of cardiac fibroblasts by 30% compared with cells without HB-EGF treatment. HB-EGF-induced proliferation was completely diminished in the presence of Rapa. These results suggest that HB-EGF induced heart fibrosis and proliferation of cardiac fibroblasts occurs through activation of the Akt/mTor/p70s6k pathway.</p> </div

    Rapa inhibited HB-EGF induced heart interstitial fibrosis and synthesis of collagen I in vivo.

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    <p>The mice were treated with vehicle or 5 mg/kg Rapa every second day by intraperitoneal injection for five times. Masson staining (A, <i>n</i> = 3) and western immunoblot (B, <i>n</i> = 3) were detected. Original magnification ×200.</p
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