Irreversibility of cellular senescence: dual roles of p16(INK4a)/Rb-pathway in cell cycle control

The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses. In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells. However, in human cells, once pRb is fully activated by p16(INK4a), senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16(INK4a)/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells. Here, we discuss the molecular mechanism underlying the irreversibility of senescence cell cycle arrest and its potential towards tumor suppression

The systematic investigations of high-pressure polymorphs in shocked L type ordinary chondrites

第6回極域科学シンポジウム[OA] 南極隕石11月16日（月）　国立国語研究所 2階 講

Real-time in vivo imaging of p16Ink4a gene expression: a new approach to study senescence stress signaling in living animals

Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16INK4a. To date, much of our current knowledge of how human p16INK4a gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16INK4a gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16INK4a gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. To eliminate any potential problems arising from tissue culture imposed stress, we have recently developed a bioluminescence imaging (BLI) system for non-invasive and real-time analysis of human p16INK4a gene expression in the context of a living animal. Here, we discuss the molecular mechanisms that direct p16INK4a gene expression in vivo and its potential for tumor suppression

Phase relations and melting of carbonated peridotite between 10 and 20GPa: a proxy for alkali- and CO2-rich silicate melts in the deep mantle

We determined the melting phase relations, melt compositions, and melting reactions of carbonated peridotite on two carbonate-bearing peridotite compositions (ACP: alkali-rich peridotite+5.0wt% CO2 and PERC: fertile peridotite+2.5 wt% CO2) at 10-20GPa and 1,500-2,100°C and constrain isopleths of the CO2 contents in the silicate melts in the deep mantle. At 10-20GPa, near-solidus (ACP: 1,400-1,630°C) carbonatitic melts with40wt% CO2 gradually change to carbonated silicate melts with>25wt% SiO2 and15GPa. Similar to hydrous peridotite, majorite garnet is a liquidus phase in carbonated peridotites (ACP and PERC) at 10-20GPa. The liquidus is likely to be at~2,050°C or higher at pressures of the present study, which gives a melting interval of more than 670°C in carbonated peridotite systems. Alkali-rich carbonated silicate melts may thus be produced through partial melting of carbonated peridotite to 20GPa at near mantle adiabat or even at plume temperature. These alkali- and CO2-rich silicate melts can percolate upward and may react with volatile-rich materials accumulate at the top of transition zone near 410-km depth. If these refertilized domains migrate upward and convect out of the zone of metal saturation, CO2 and H2O flux melting can take place and kimberlite parental magmas can be generated. These mechanisms might be important for mantle dynamics and are potentially effective metasomatic processes in the deep mantle

Petrography of Yamato 984028 lherzolitic shergottite and its melt vein: Implications for its shock metamorphism and origin of the vein

AbstractYamato 984028 (Y984028) is a newly identified lherzolitic shergottite, recovered from the Yamato Mountains, Antarctica, in 1999. As part of a consortium study, we conducted petrographic observations of Y984028 and its melt vein in order to investigate its shock metamorphism. The rock displays the typical non-poikilitic texture of lherzolitic shergottite, characterized by a framework of olivine, minor pyroxene (pigeonite and augite), and interstitial maskelynite. Shock metamorphic features include irregular fractures in olivine and pyroxene, shock-induced twin-lamellae in pyroxene, and the complete conversion of plagioclase to maskelynite, features consistent with those found in other lherzolitic shergottites. The melt vein is composed of coarse mineral fragments (mainly olivine) entrained in a matrix of fine-grained euhedral olivine (with several modes of compositional zoning) and interstitial glassy material. Some coarse olivine fragments consist of an assemblage of fine-grained euhedral to subhedral olivine crystals, suggesting shock-induced fragmentation, recrystallization, and/or a process of sintering. The implication is that the fine-grained olivine crystals in the matrix of the melt vein represent complicated crystallization environments and histories

The p16INK4a-RB pathway : molecular link between cellular senescence and tumor suppression

The p16INK4a tumor suppressor protein functions as an inhibitor ofCDK4andCDK6, the D-type cyclin-dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein, RB. Thus, p16INK4a has the capacity to arrest cells in the G1-phase of the cell cycle and its probable physiological role is in the implementation of irreversible growth arrest termed cellular senescence. Cellular senescence is a state of permanent growth arrest that can be induced by a variety of stresses such as DNA-damage and aberrant mitogenic signaling in human primary cells. In contrast to normal cells, the function of the p16INK4a gene or its downstream mediators is frequently deregulated in many types of human cancers, illustrating the importance of cellular senescence in tumor suppression. Here we discuss the molecular mechanisms that direct cellular senescence and reveal its potential for tumor suppression

Silicon self-diffusion in wadsleyite: Implications for rheology of the mantle transition zone and subducting plates

/s] exp (À248 [kJ/mol]/RT), respectively. Si diffusion rates in wadsleyite are about 5 orders of magnitude slower than Mg-Fe interdiffusion rates at 1400°C. Assuming that Si is the slowest diffusing species in wadsleyite, the geophysical model of the viscosity in the mantle transition zone can be explained by diffusion creep in wadsleyite for a grain size of about 0.5-5 mm. Some portions in cold subducting slabs, where the grain size reduces to less than 1 mm after the olivinespinel transformation, become weaker than the surrounding mantle

The investigation of back-transformation mechanisms of ringwoodite and majorite in the Yamato 75267 H6

The Tenth Symposium on Polar Science/Special session: [OA] Antarctic meteorites, Thur. 5 Dec. / 3F Multipurpose conference room, National Institute of Polar Researc