During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between t...During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution ofcytokinesis. Central spindle organization requires mitotic kinesins, the chromosomal passenger protein complex, and microtubule bundling protein PRC 1. PRC 1 is phosphorylated by Cdc2 at Thr470 and Thr481 during mitosis. However, the functional relevance of PRC 1 phosphorylation at Thr470 has remained elusive. Here we show that expression of the non-phosphorylatable mutant PRC 1T470A but not the phospho-mimicking mutant PRC 1^T470E causes aberrant organization of the central spindle. Immunoprecipitation experiment indicates that both PRC 1^T470A and PRC 1^T470E mutant proteins associate with wild-type PRC 1, suggesting that phosphorylation of Thr470 does not alter PRC 1 self-association. In addition, in vitro co-sedimentation experiment showed that PRC 1 binds to microtubule independent of the phosphorylation state of Thr470. Gel-filtration experiment suggested that phosphorylation of Thr470 promotes oligomerization of PRC 1. Given the fact that prevention of the Thr470 phosphorylation inhibits PRC 1 oligomerization in vitro and causes an aberrant organization of central spindle in vivo, we propose that this phosphorylation-dependent PRC 1 oligomerization ensures that central spindle assembly occurs at the appropriate time in the cell cycle.展开更多
Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 a...Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.展开更多
The data of this paper mainly include statistics,field survey data and MODIS remote sensing image data. This paper estimates the aboveground biomass of grassland and theoretical livestock carrying capacity of natural ...The data of this paper mainly include statistics,field survey data and MODIS remote sensing image data. This paper estimates the aboveground biomass of grassland and theoretical livestock carrying capacity of natural grassland in Hangjin Banner and draws a grass- livestock balance table in accordance with the actual and theoretical livestock carrying capacity of natural grassland. Studies have shown that the grass and livestock balance is good in Hangjin Banner,and the overloading rate is 1. 5%; there was no overloading in 2010 and 2011.展开更多
Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying ...Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.展开更多
Ezrin,a membrane–cytoskeleton linker protein,plays an essential role in cell polarity establishment,cell migration,and division.Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by pro...Ezrin,a membrane–cytoskeleton linker protein,plays an essential role in cell polarity establishment,cell migration,and division.Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by promoting cancer cell survivor and promotes intrahepatic metastasis via cell migration.However,it was less characterized whether there are additional post-translational modifications and/or post-translational crosstalks on ezrin underlying context-dependent breast cancer cell migration and invasion.Here we show that ezrin is acetylated by p300/CBP-associated factor(PCAF)in breast cancer cells in response to CCL18 stimulation.Ezrin physically interacts with PCAF and is a cognate substrate of PCAF.The acetylation site of ezrin was mapped by mass spectrometric analyses,and dynamic acetylation of ezrin is essential for CCL18-induced breast cancer cell migration and invasion.Mechanistically,the acetylation reduced the lipid-binding activity of ezrin to ensure a robust and dynamic cycling between the plasma membrane and cytosol in response to CCL18 stimulation.Biochemical analyses show that ezrin acetylation prevents the phosphorylation of Thr567.Using atomic force microscopic measurements,our study revealed that acetylation of ezrin induced its unfolding into a dominant structure,which prevents ezrin phosphorylation at Thr567.Thus,these results present a previously undefined mechanism by which CCL18-elicited crosstalks between the acetylation and phosphorylation on ezrin control breast cancer cell migration and invasion.This suggests that targeting PCAF signaling could be a potential therapeutic strategy for combating hyperactive ezrin-driven cancer progression.展开更多
基金National Natural Science Foundation of China （39925018, 90508002 , 30121001） Chinese Academy of Science （KSCX 1-R65 and RSCX2-H10）+2 种基金 National Basic Research Program of China （973 project, 2002CB713700） American Cancer Society （RPG-99-173-01） a Gcc Breast Cancer Research award and National Institutes of Health grants DK56292 and CA89019 to XY （a GCC Eminent Scholar） and NS36194 （JW）.
文摘During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution ofcytokinesis. Central spindle organization requires mitotic kinesins, the chromosomal passenger protein complex, and microtubule bundling protein PRC 1. PRC 1 is phosphorylated by Cdc2 at Thr470 and Thr481 during mitosis. However, the functional relevance of PRC 1 phosphorylation at Thr470 has remained elusive. Here we show that expression of the non-phosphorylatable mutant PRC 1T470A but not the phospho-mimicking mutant PRC 1^T470E causes aberrant organization of the central spindle. Immunoprecipitation experiment indicates that both PRC 1^T470A and PRC 1^T470E mutant proteins associate with wild-type PRC 1, suggesting that phosphorylation of Thr470 does not alter PRC 1 self-association. In addition, in vitro co-sedimentation experiment showed that PRC 1 binds to microtubule independent of the phosphorylation state of Thr470. Gel-filtration experiment suggested that phosphorylation of Thr470 promotes oligomerization of PRC 1. Given the fact that prevention of the Thr470 phosphorylation inhibits PRC 1 oligomerization in vitro and causes an aberrant organization of central spindle in vivo, we propose that this phosphorylation-dependent PRC 1 oligomerization ensures that central spindle assembly occurs at the appropriate time in the cell cycle.
基金Supported by the National Natural Sciences Foundation of China(30370443)
文摘Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.
基金Supported by Land Ecological Survey and Assessment Project in Western Energy Development Zone and Newly Reclaimed Area(1211410781016)Industrial Innovation(Entrepreneurship)Talent Team in Inner Mongolia
文摘The data of this paper mainly include statistics,field survey data and MODIS remote sensing image data. This paper estimates the aboveground biomass of grassland and theoretical livestock carrying capacity of natural grassland in Hangjin Banner and draws a grass- livestock balance table in accordance with the actual and theoretical livestock carrying capacity of natural grassland. Studies have shown that the grass and livestock balance is good in Hangjin Banner,and the overloading rate is 1. 5%; there was no overloading in 2010 and 2011.
基金This work was supported in part by the National NaturalScience Foundation of China(31430054,31320103904,31621002,31671405,31601097,91854203,91753000,and91853115)'Strategic Priority Research Program'of the ChineseAcademy of Sciences(XDB19000000)+2 种基金the National Key Researchand Development Program of China(2017YFA0503600 and2016YFA-0100500)MOE Innovative Team project(IRT_17R102)and the US National Institutes of Health(CA164133,DK56292,and DK115812).
文摘Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.
基金This work was supported in part by grants from the National Natural Science Foundation of China(81630080,31430054,91854203,31301105,31320103904,31621002,31671405,91853115,21922706,81572283,31271518,31471275,and 31870759)National Key Research and Development Program of China(2017YFA0503600 and 2016YFA0100500)+2 种基金Ministry of Education(IRT_17R102 and 20113402130010)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB19000000)Central University Grants WK2340000066.
文摘Ezrin,a membrane–cytoskeleton linker protein,plays an essential role in cell polarity establishment,cell migration,and division.Recent studies show that ezrin phosphorylation regulates breast cancer metastasis by promoting cancer cell survivor and promotes intrahepatic metastasis via cell migration.However,it was less characterized whether there are additional post-translational modifications and/or post-translational crosstalks on ezrin underlying context-dependent breast cancer cell migration and invasion.Here we show that ezrin is acetylated by p300/CBP-associated factor(PCAF)in breast cancer cells in response to CCL18 stimulation.Ezrin physically interacts with PCAF and is a cognate substrate of PCAF.The acetylation site of ezrin was mapped by mass spectrometric analyses,and dynamic acetylation of ezrin is essential for CCL18-induced breast cancer cell migration and invasion.Mechanistically,the acetylation reduced the lipid-binding activity of ezrin to ensure a robust and dynamic cycling between the plasma membrane and cytosol in response to CCL18 stimulation.Biochemical analyses show that ezrin acetylation prevents the phosphorylation of Thr567.Using atomic force microscopic measurements,our study revealed that acetylation of ezrin induced its unfolding into a dominant structure,which prevents ezrin phosphorylation at Thr567.Thus,these results present a previously undefined mechanism by which CCL18-elicited crosstalks between the acetylation and phosphorylation on ezrin control breast cancer cell migration and invasion.This suggests that targeting PCAF signaling could be a potential therapeutic strategy for combating hyperactive ezrin-driven cancer progression.
