CDK‐mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC‐driven transcription and tumourigenesis and predicts poor survival in breast cancer

SCF (Skp1/Cul1/F‐box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F‐box protein, FBXO28 that controls MYC‐dependent transcription by non‐proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2‐mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F‐box mutant unable to support MYC ubiquitylation results in an impairment of MYC‐driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK‐FBXO28‐MYC axis as a potential molecular drug target in MYC‐driven cancers, including breast cancer

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Preparative separation of C19-diterpenoid alkaloids from Aconitum carmichaelii Debx by pH‑zone-refining counter-current chromatography

The technique of pH-zone-refining counter-current chromatography was successfully applied to preparatively separate three C19-diterpenoid alkaloids from the crude extracts of Aconitum carmichaelii for the first time using a two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v). Mesaconitine (I), hypaconitine (II), and deoxyaconitine (III) were obtained from 2.5 g of the crude alkaloids in a one-step separation; the yields were 4.16%, 16.96%, and 5.05%, respectively. The purities of compounds I, II, and III were 93.0%, 95%, and 96%, respectively, as determined by HPLC. The chemical structures of the three compounds were identified by electrospray ionization mass spectrometry (ESI-MS) and NMR

enhancedelectrocatalyticperformanceofultrathinptnialloynanowiresforoxygenreductionreaction

In this paper, ultrathin Pt nanowires （Pt NWs） and PtNi alloy nanowires （PtNi NWs） supported on carbon were synthesized as electrocatalysts for oxygen reduction reaction （ORR）. Pt and PtNi NWs catalysts composed of interconnected nanoparticles were prepared by using a soft template method with CTAB as the surface active agent. The physical characterization and electrocatalytic perfor- mance of Pt NWs and PtNi NWs catalysts for ORR were investigated and the results were compared with the commercial Pt/C catalyst. The atomic ratio of Pt and Ni in PtNi alloy was approximately 3 to 1. The results show that after alloying with Ni, the binding energy of Pt shifts to higher values, indicating the change of its electronic structure, and that Pt3Ni NWs catalyst has a significantly higher electrocatalytic activity and good stability for ORR as compared to Pt NWs and even Pt/C catalyst. The enhanced electrocatalytic activity of Pt3Ni NWs catalyst is mainly resulted from the downshifted-band center of Pt caused by the interaction between Pt and Ni in the alloy, which facilitates the desorption of oxygen containing species （Oads or OHads） and the release of active sites

Facile Synthesis of Nanoporous Pt-Encapsulated Ir Black as a Bifunctional Oxygen Catalyst via Modified Polyol Process at Room Temperature

The exploitation of a bifunctional oxygen catalyst with high efficiency is crucial for a high-performance unitized regenerative fuel cell (URFC). However, the existing bifunctional oxygen catalysts still suffer from low catalytic efficiency due to sluggish oxygen electrode reactions toward oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, we report on a facile synthesis of nanoporous Pt-encapsulated Ir black with Pt/Ir mass ratio of 55/45 (Pt-55@Ir-45) via a newly modified polyol process at room temperature with the aid of water. The resulting Pt-55@Ir-45 catalyst demonstrated to be highly efficient and robust for both ORR and OER, relative to a mixture of commercial Pt and Ir black with Pt/Ir mass ratio of 50/50 (Pt-50/Ir-50). Mass activity of Pt-55@Ir-45 presented an 8.7- and 1.6-fold increase toward ORR and OER, respectively, compared with the Pt-50/Ir-50 catalyst. The enhanced bifunctional performance was rationalized in terms of the maximized Pt utilization, achieved by the excellent dispersion of Pt nanoparticles, and the nanoporous Pt layer constructing a conductive network without impeding the transport of oxygen and water molecules. Our work demonstrates an effective means to encapsulate nanoporous Pt layers on Ir black for the fabrication of bifunctional oxygen catalysts

Self-Sacrificial Template Synthesis of a Nitrogen-Doped Microstructured Carbon Tube as Electrocatalyst for Oxygen Reduction

The development of low-cost, efficient and stable electrocatalysts for the oxygen reduction reaction (ORR) is desirable but remains a great challenge. We report a self-sacrificial template synthesis approach for nitrogen-doped hollow carbon microtubes as electrocatalyst for ORR. Typically, Fe-MIL (Materiaux de l'Institute Lavosier) nanocrystals cast as self-sacrificial template. Polyaniline (PANI) was in situ-synthesized and deposited on the surface of Fe-MIL nanocrystals. By a two-step pyrolysis of the MIL-101 (Fe)@PANI hybrids, unique microstructured carbon tubes with Fe3O4 nanoparticles encapsulated inside the wall were fabricated after the self-sacrificial template decomposed. The optimized C-PANI-MIL-2 catalyst exhibits a high onset potential of 1.0 V in alkaline media. Out of the negative effect of the disruption of metal-organic frameworks (MOF) morphology, the ingenious catalytic activities may be ascribed to the well-defined microtube architecture with a high accessible surface area, the existence of FeN2+2/FeN4 and rich active nitrogen atoms. Moreover, C-PANI-MIL-2 exhibited excellent methanol tolerance and durability compared to a commercial Pt/C catalyst in both electrolytes. This work may provide a new strategy for the design and preparation of microstructured non-precious metal based catalysts supported on hollow carbon tubes for fuel cells

Facile synthesis of Pt-decorated Ir black as a bifunctional oxygen catalyst for oxygen reduction and evolution reactions

Pt-Decorated Ir black (Pt@Ir) nanoparticles with two varying Pt mass fractions (Pt-4@Ir-96 and Pt-16@Ir-84) were generated by a facile method in water with the aid of Ir black. The Pt@Ir nanoparticles were investigated as a bifunctional oxygen catalysts for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in acidic medium. Benefiting from the good dispersion of ultrafine Pt nanodots on the Ir black surface and the synergistic effect between the Pt and underlying Ir atoms, Pt@Ir nanoparticles have exhibited outstanding ORR activity and comparable OER performance in comparison with commercial Ir black. In particular, Pt-16@Ir-84 shows an ORR mass activity of 2.6 times that of commercial Pt black and exhibits much better bifunctional performances than a mixture of Pt black and Ir black with a Ir/Pt mass ratio of 50/50 (Pt50Ir50). Our work highlights the effectiveness of decorating Ir black with Pt nanodots to fabricate bifunctional oxygen catalysts

carbonsupportedultrafineptnanoparticlesmodifiedwithtraceamountsofcobaltasenhancedoxygenreductionreactioncatalystsforprotonexchangemembranefuelcells

To accelerate the kinetics of the oxygen reduction reaction (orr) in proton exchange membrane fuel cells, ultrafine pt nanoparticles modified with trace amounts of cobalt were fabricated and decorated on carbon black through a strategy involving modified glycol reduction and chemical etching. the obtained pt36co/c catalyst exhibits a much larger electrochemical surface area (ecsa) and an improved orr electrocatalytic activity compared to commercial pt/c. moreover, an electrode prepared with pt36co/c was further evaluated under h-2-air single cell test conditions, and exhibited a maximum specific power density of 10.27 w mg(pt)(-1),which is 1.61 times higher than that of a conventional pt/c electrode and also competitive with most state-of-the-art pt -based architectures. in addition, the changes in ecsa, power density, and reacting resistance during the accelerated degradation process further demonstrate the enhanced durability of the pt36co/c electrode. the superior performance observed in this work can be attributed to the synergy between the ultrasmall size and homogeneous distribution of catalyst nanoparticles, bimetallic ligand and electronic effects, and the dissolution of unstable co with the rearrangement of surface structure brought about by acid etching. furthermore, the accessible raw materials and simplified operating procedures involved in the fabrication process would result in great cost-effectiveness for practical applications of pemfcs. (c) 2019, dalian institute of chemical physics, chinese academy of sciences. published by elsevier b.v. all rights reserved

carbonsupportedultrafineptnanoparticlesmodifiedwithtraceamountsofcobaltasenhancedoxygenreductionreactioncatalystsforprotonexchangemembranefuelcells

To accelerate the kinetics of the oxygen reduction reaction (orr) in proton exchange membrane fuel cells, ultrafine pt nanoparticles modified with trace amounts of cobalt were fabricated and decorated on carbon black through a strategy involving modified glycol reduction and chemical etching. the obtained pt36co/c catalyst exhibits a much larger electrochemical surface area (ecsa) and an improved orr electrocatalytic activity compared to commercial pt/c. moreover, an electrode prepared with pt36co/c was further evaluated under h-2-air single cell test conditions, and exhibited a maximum specific power density of 10.27 w mg(pt)(-1),which is 1.61 times higher than that of a conventional pt/c electrode and also competitive with most state-of-the-art pt -based architectures. in addition, the changes in ecsa, power density, and reacting resistance during the accelerated degradation process further demonstrate the enhanced durability of the pt36co/c electrode. the superior performance observed in this work can be attributed to the synergy between the ultrasmall size and homogeneous distribution of catalyst nanoparticles, bimetallic ligand and electronic effects, and the dissolution of unstable co with the rearrangement of surface structure brought about by acid etching. furthermore, the accessible raw materials and simplified operating procedures involved in the fabrication process would result in great cost-effectiveness for practical applications of pemfcs. (c) 2019, dalian institute of chemical physics, chinese academy of sciences. published by elsevier b.v. all rights reserved