The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved ...The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.展开更多
From the constitutive model with generalized force fields for a viscoelastic body with damage, the differential equations of motion for thin and thick plates with damage are derived under arbitrary boundary conditions...From the constitutive model with generalized force fields for a viscoelastic body with damage, the differential equations of motion for thin and thick plates with damage are derived under arbitrary boundary conditions. The convolution-type functionals for the bending of viscoelastic thin and thick plates with damage are presented, and the corresponding generalized variational principles are given. From these generalized principles, all the basic equations of the displacement and damage variables and initial and boundary conditions can be deduced. As an example, we compare the difference between the dynamical properties of plates with and without damage and consider the effect of damage on the dynamical properties of plates.展开更多
With 40 years of development, bio-macromolecule cryo-electron microscopy（cryo-EM） has completed its revolution in terms of resolution and currently plays a highly important role in structural biology study. Accordin...With 40 years of development, bio-macromolecule cryo-electron microscopy（cryo-EM） has completed its revolution in terms of resolution and currently plays a highly important role in structural biology study. According to different specimen states, cryo-EM involves three specific techniques： single-particle analysis（SPA）, electron tomography and subtomogram averaging, and electron diffraction. None of these three techniques have realized their full potential for solving the structures of bio-macromolecules and therefore need additional development. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which include the air–water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimens, and electron radiation damage. Furthermore, potential solutions of these bottlenecks worthy of further investigation are proposed and discussed.展开更多
基金supported by grants from the National Natural Science Foundation of China(8120223181273116+2 种基金81430079)the Science and Technology Program of Guangdong Bureau of Science and TechnologyChina(2013B021800069)
文摘The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.
基金Project supported by the National Natural Sciences Foundation of China (No. 10272069) the Shanghai Key Subject Program.
文摘From the constitutive model with generalized force fields for a viscoelastic body with damage, the differential equations of motion for thin and thick plates with damage are derived under arbitrary boundary conditions. The convolution-type functionals for the bending of viscoelastic thin and thick plates with damage are presented, and the corresponding generalized variational principles are given. From these generalized principles, all the basic equations of the displacement and damage variables and initial and boundary conditions can be deduced. As an example, we compare the difference between the dynamical properties of plates with and without damage and consider the effect of damage on the dynamical properties of plates.
基金supported by the Science Funds from the Chinese Academy of Sciences(Grant Nos.ZDKYYQ20170002 and XDB08030202)the Science Funds from the Ministry of Science and Technology of China(Grant Nos.2017YFA0504700 and 2014CB910700)
文摘With 40 years of development, bio-macromolecule cryo-electron microscopy（cryo-EM） has completed its revolution in terms of resolution and currently plays a highly important role in structural biology study. According to different specimen states, cryo-EM involves three specific techniques： single-particle analysis（SPA）, electron tomography and subtomogram averaging, and electron diffraction. None of these three techniques have realized their full potential for solving the structures of bio-macromolecules and therefore need additional development. In this review, the current existing bottlenecks of cryo-EM SPA are discussed with theoretical analysis, which include the air–water interface during specimen cryo-vitrification, bio-macromolecular conformational heterogeneity, focus gradient within thick specimens, and electron radiation damage. Furthermore, potential solutions of these bottlenecks worthy of further investigation are proposed and discussed.
