51 research outputs found

    Renormalization Group Approach to Einstein Equation in Cosmology

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    The renormalization group method has been adapted to the analysis of the long-time behavior of non-linear partial differential equation and has demonstrated its power in the study of critical phenomena of gravitational collapse. In the present work we apply the renormalization group to the Einstein equation in cosmology and carry out detailed analysis of renormalization group flow in the vicinity of the scale invariant fixed point in the spherically symmetric and inhomogeneous dust filled universe model.Comment: 16 pages including 2 eps figures, RevTe

    Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

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    Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells

    Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells

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    Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells. NADPH oxidase inhibition using apocynin or small interfering RNAs (siRNAs) abrogated the induction of IL-8 and ROS in TP-expressing cancer cells. Meanwhile, thymidine catabolism induced by TP increased the levels of NADPH and intermediates of the pentose phosphate pathway (PPP). Both siRNA knockdown of glucose 6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme in PPP, and a G6PD inhibitor, dihydroepiandrosterone, reduced TP-induced ROS production. siRNA downregulation of 2-deoxy-D-ribose 5-phosphate (DR5P) aldolase, which is needed for DR5P to enter glycolysis, also suppressed the induction of NADPH and IL-8 in TP-expressing cells. These results suggested that TP-mediated thymidine catabolism increases the intracellular NADPH level via the PPP, which enhances the production of ROS by NADPH oxidase and activates its downstream signalling

    Fundamental physics activities with pulsed neutron at J-PARC(BL05)

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    "Neutron Optics and Physics (NOP/ BL05)" at MLF in J-PARC is a beamline for studies of fundamental physics. The beamline is divided into three branches so that different experiments can be performed in parallel. These beam branches are being used to develop a variety of new projects. We are developing an experimental project to measure the neutron lifetime with total uncertainty of 1 s (0.1%). The neutron lifetime is an important parameter in elementary particle and astrophysics. Thus far, the neutron lifetime has been measured by several groups; however, different values are obtained from different measurement methods. This experiment is using a method with different sources of systematic uncertainty than measurements conducted to date. We are also developing a source of pulsed ultra-cold neutrons (UCNs) produced from a Doppler shifter are available at the unpolarized beam branch. We are developing a time focusing device for UCNs, a so called "rebuncher", which can increase UCN density from a pulsed UCN source. At the low divergence beam branch, an experiment to search an unknown intermediate force with nanometer range is performed by measuring the angular dependence of neutron scattering by noble gases. Finally the beamline is also used for the research and development of optical elements and detectors. For example, a position sensitive neutron detector that uses emulsion to achieve sub-micrometer resolution is currently under development. We have succeeded in detecting cold and ultra-cold neutrons using the emulsion detector.Comment: 9 pages, 5 figures, Proceedings of International Conference on Neutron Optics (NOP2017

    Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95

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    Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals
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