The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C

The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons. These ABBA motifs flank a KEN box to form a cassette that is highly conserved through evolution, both in the arrangement and spacing of the ABBA-KEN-ABBA motifs, and association with the amino-terminal KEN box required to form the MCC. We propose that the ABBA-KEN-ABBA cassette holds the MCC onto the APC/C by binding the two Cdc20 molecules in the MCC-APC/C complex.This work was supported by an SFI Starting Investigator Research Grant (13/SIRG/2193) to N.E.D. and a CR UK Programme grant C29/A13678 to J.P. J.P. acknowledges the financial support of Wellcome Trust Grant 092096 and CR UK Grant C6946/A14492 core support to the Gurdon Institute

Urazine – a Long Established Heterocycle and Energetic Chameleon

The five‐membered heterocycle urazine is investigated as a useful precursor of energetic materials. A variety of salt and complexes as well as a trinitroethyl derivative is presented. The compounds were thoroughly characterized including their thermal stability and sensitivity values. Furthermore, for potential applications, small‐scale shock reactivity test (SSRT), hot needle, hot plate, and laser ignition tests were performed

Enhanced CO resistance of Pd/SSZ-13 for passive NOx adsorption

Passive NOx adsorption (PNA) is a novel technology to control NOx emissions during cold start. However, the recent generation of PNA material, Pd/zeolite, suffers from major degradation under high CO concentrations. In this work, we developed a novel form of Pd/SSZ-13 by using a freeze-drying process after incipient wetness impregnation. This Pd/SSZ-13 showed a better stability than the sample synthesized by the common process. Several characterization measurements were conducted and it was found that the Pd sites on the freeze-dried sample were more resistant towards CO-induced agglomeration. By combing in-situ characterization and kinetic modeling, we found that the freeze-dried Pd/SSZ-13 had more ion-exchanged Pd sites, which provided greater resistance towards the CO-induced Ostwald ripening process, and consequently suppressed the sintering behavior under a high CO concentration. This material offers a potentially improved stability of PNAs under extremely high CO concentration pulses from incomplete diesel combustion during engine cold start

Kinetic modeling of CO assisted passive NOx adsorption on Pd/SSZ-13

Passive NOx adsorption (PNA) has been recently developed as a promising technology for controlling the NOx emissions during the cold start period. In this work, we illustrate a CO-assisted mechanism by combining experimental and kinetic modeling studies. Pd/SSZ-13 has been synthesized, characterized and evaluated as a PNA in low-temperature NOx adsorption and temperature program desorption cycles, to represent multiple cold start periods. The gas compositions were also systemically changed, where both the effect of varying NOx and CO feed was evaluated in the presence of high water and oxygen contents. A kinetic model was developed to simulate the profiles of NO and NO2, including three initial Pd sites (Z-Pd(II)Z-, Z-[Pd(II)OH]+ and PdO). It is concluded from XPS and in situ DRIFTS experiments, flow reactor measurements and modelling observations that CO reduces Pd(II) species to Pd(I)/Pd(0) species, which increases the stability of the stored NOx species, resulting in a release above the urea dosing temperature. The model could well describe the experimental features, including the effect of CO. In addition, the model was used for full-scale catalytic converter simulations

Insight into CO induced degradation mode of Pd/SSZ-13 in NOx adsorption and release: Experiment and modeling

Passive NOx adsorption (PNA) on Pd zeolites is an important technique to remove NOx during the cold start of the engine. However, the stability of Pd zeolites under high concentrations of CO is still challenging in multiple cold starts of an engine. Herein, we illustrate the CO-induced degradation mechanism of Pd zeolite by combining experiments and kinetic models. Pd/SSZ-13 has been used in multicycle processes containing NOx adsorption at low temperature and temperature programmed desorption, which represents the PNA degradation in multiple cold start periods. A kinetic model was developed to describe the NOx storage and degradation behavior of Pd/SSZ-13. Both experimental and modelling observations suggested that two Pd sintering modes are occurring under high CO concentration (4000 ppm), namely Ostwald ripening and particle migration. Apart from the degradation behavior, this model is also adequate for describing multi-cycle NOx storage and release behavior under low CO concentration

Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences