p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.T...p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.The activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53.This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis.Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress.The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and RPL11.These results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.展开更多
In this work, a second order smoothed particle hydrodynamics is derived for the study of relativistic heavy ion collisions. The hydrodynamical equation of motion is formulated in terms of the variational principle. In...In this work, a second order smoothed particle hydrodynamics is derived for the study of relativistic heavy ion collisions. The hydrodynamical equation of motion is formulated in terms of the variational principle. In order to describe the fluid of high energy density but of low baryon density, the entropy is taken as the base quantity for the interpolation. The smoothed particle hydrodynamics algorithm employed in this study is of the second order, which guarantees better particle consistency. Furthermore, it is shown that the variational principle preserves the translational invariance of the system, and therefore improves the accuracy of the method. A brief discussion on the potential implications of the model in heavy ion physics as well as in general relativity are also presented.展开更多
The present work investigates the entropy and the excitation inversion of a coupled system that consists of a qubit represented by a Cooper pair box(CPB) interacting with a transmission line working as a circuit quant...The present work investigates the entropy and the excitation inversion of a coupled system that consists of a qubit represented by a Cooper pair box(CPB) interacting with a transmission line working as a circuit quantum electrodynamics(CQED). The proposed scheme uses the Buck-Sukumar model with a time dependent frequency in the presence of losses to study the evolution of the entropy and the excitation inversion of the system. We have shown that the CQED is much more sensitive to the presence of losses than the CPB. The results also show that it is possible to monitor properties of the subsystems through appropriate choices of the time-dependent parameters.展开更多
In this work we consider black hole solutions to Einstein’s theory coupled to a nonlinear powerlaw electromagnetic field with a fixed exponent value.We study the extended phase space thermodynamics in canonical and g...In this work we consider black hole solutions to Einstein’s theory coupled to a nonlinear powerlaw electromagnetic field with a fixed exponent value.We study the extended phase space thermodynamics in canonical and grand canonical ensembles,where the varying cosmological constant plays the role of an effective thermodynamic pressure.We examine thermodynamical phase transitions in such black holes and find that both first-and second-order phase transitions can occur in the canonical ensemble while,for the grand canonical ensemble,Hawking-Page and second-order phase transitions are allowed.展开更多
文摘p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting partners.The hierarchical order and subcellular location of these events are still poorly understood.The activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of p53.This is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 synthesis.Here we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic stress.The ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and RPL11.These results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.
基金financial support from Funda o de Amparo à Pesquisa do Estado de So Paulo (FAPESP)Funda o de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)+2 种基金Fundao de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordena o de Aperfei oamento de Pessoal de Nível Superior (CAPES)
文摘In this work, a second order smoothed particle hydrodynamics is derived for the study of relativistic heavy ion collisions. The hydrodynamical equation of motion is formulated in terms of the variational principle. In order to describe the fluid of high energy density but of low baryon density, the entropy is taken as the base quantity for the interpolation. The smoothed particle hydrodynamics algorithm employed in this study is of the second order, which guarantees better particle consistency. Furthermore, it is shown that the variational principle preserves the translational invariance of the system, and therefore improves the accuracy of the method. A brief discussion on the potential implications of the model in heavy ion physics as well as in general relativity are also presented.
基金supports by the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)the FAPEG-CNPq,Brazilian AgenciesRosemberg Fortes Nunes Rodrigues for Fig.1
文摘The present work investigates the entropy and the excitation inversion of a coupled system that consists of a qubit represented by a Cooper pair box(CPB) interacting with a transmission line working as a circuit quantum electrodynamics(CQED). The proposed scheme uses the Buck-Sukumar model with a time dependent frequency in the presence of losses to study the evolution of the entropy and the excitation inversion of the system. We have shown that the CQED is much more sensitive to the presence of losses than the CPB. The results also show that it is possible to monitor properties of the subsystems through appropriate choices of the time-dependent parameters.
基金supported by ANID Chile through FONDECYT Grant No.1210635(J S)support from the Dirección de Investigación y Desarrollo de la Universidad de La Serena,Grant No.PR18142supported in part by NNSFC under Grant No.12075202。
文摘In this work we consider black hole solutions to Einstein’s theory coupled to a nonlinear powerlaw electromagnetic field with a fixed exponent value.We study the extended phase space thermodynamics in canonical and grand canonical ensembles,where the varying cosmological constant plays the role of an effective thermodynamic pressure.We examine thermodynamical phase transitions in such black holes and find that both first-and second-order phase transitions can occur in the canonical ensemble while,for the grand canonical ensemble,Hawking-Page and second-order phase transitions are allowed.