B3LYP Study on Reduction Mechanisms from O2 to H2O at the Catalytic Sites of Fully Reduced and Mixed-Valence Bovine Cytochrome c Oxidases

Reduction mechanisms of oxygen molecule to water molecules in the fully reduced (FR) and mixed-valence (MV) bovine cytochrome c oxidases (CcO) have been systematically examined based on the B3LYP calculations. The catalytic cycle using four electrons and four protons has been also shown consistently. The MV CcO catalyses reduction to produce one water molecule, while the FR CcO catalyses to produce two water molecules. One water molecule is added into vacant space between His240 and His290 in the catalytic site. This water molecule constructs the network of hydrogen bonds of Tyr244, farnesyl ethyl, and Thr316 that is a terminal residue of the K-pathway. It plays crucial roles for the proton transfer to the dioxygen to produce the water molecules in both MV and FR CcOs. Tyr244 functions as a relay of the proton transfer from the K-pathway to the added water molecule, not as donors of a proton and an electron to the dioxygen. The reduction mechanisms of MV and FR CcOs are strictly distinguished. In the FR CcO, the Cu atom at the CuB site maintains the reduced state Cu(I) during the process of formation of first water molecule and plays an electron storage. At the final stage of formation of first water molecule, the Cu(I) atom releases an electron to Fe-O. During the process of formation of second water molecule, the Cu atom maintains the oxidized state Cu(II). In contrast with experimental proposals, the K-pathway functions for formation of first water molecule, while the D-pathway functions for second water molecule. The intermediates, PM, PR, F, and O, obtained in this work are compared with those proposed experimentally

DNA Lesions Induced by Replication Stress Trigger Mitotic Aberration and Tetraploidy Development

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress

Selective phenol recovery via simultaneous hydrogenation/ dealkylation of isopropyl- and isopropenyl-phenols employing an H2 generator combined with tandem micro-reactor GC/MS

Abstract The pyrolysis of bisphenol A (BPA), an essential process ingredient used in industry and many everyday life products, helps produce low-industrial-demand chemicals such as isopropenyl- and isopropyl-phenols (IPP and iPrP). In this study, tandem micro-reactor gas chromatography/mass spectrometry combined with an H2 generator (H2-TR-GC/MS) was employed for the first time to investigate the selective recovery of phenol via simultaneous hydrogenation/dealkylation of IPP and iPrP. After investigating the iPrP dealkylation performances of several zeolites, we obtained full iPrP conversion with over 99% phenol selectivity using the Y-zeolite at 350 °C. In contrast, when applied to IPP, the zeolite acid centres caused IPP polymerisation and subsequent IPP-polymer cracking, resulting in many byproducts and reduced phenol selectivity. This challenge was overcome by the addition of 0.3 wt% Ni on the Y-zeolite (0.3Ni/Y), which enabled the hydrogenation of IPP into iPrP and subsequent dealkylation into phenol (full IPP conversion with 92% phenol selectivity). Moreover, the catalyst deactivation and product distribution over repetitive catalytic use were successfully monitored using the H2-TR-GC/MS system. We believe that the findings presented herein could allow the recovery of phenol-rich products from polymeric waste with BPA macro skeleton

Initial Results for Science Instruments Onboard EQUULEUS During the Cruising Phase Toward the Earth Moon Lagrange Point

EQUULEUS (EQUilibriUm Lunar-Earth point 6U Spacecraft) is a spacecraft to explore the cis-lunar region including the Earth-Moon Lagrange point L2 (EML2). The spacecraft is being jointly developed by JAXA, the University of Tokyo, and several other universities in Japan. After being launched into a lunar transfer orbit by NASA\u27s SLS (Space Launch System) Artemis-1 on November 16, 2022, the spacecraft successfully performed a first Delta-V and a trajectory correction maneuver. This enabled a precise lunar flyby and successful insertion into the orbit toward EML2. Although the size of EQUULEUS is only 6U CubeSat, the spacecraft carries three different science instruments. The spacecraft can effectively demonstrate science missions during and after the flight to EML2 by using these instruments; the plasmasphere observation around the Earth by PHOENIX, the space dust flux detection in the cis-lunar region by CLOTH, and the lunar impact flash (LIF) observation at the far side of the moon by DELPHINUS. All instruments have already completed its checkout. During the cruising phase, PHOENIX conducted Earth observations and successfully identified the Earth\u27s plasmashere. CLOTH has started regular standby operations. DELPHINUS obtained impressive images such as the far side of the Moon at lunar closest approach and long-period comet, Comet ZTF. This poster presents the details of these scientific missions and the initial checkout and observation results of the science instruments