Genomic instability is a characteristic of cancer cells.In order to maintain genomic integrity,cells have evolved a complex DNA repair system to detect,signal and repair a diversity of DNA lesions.Homologous recombina...Genomic instability is a characteristic of cancer cells.In order to maintain genomic integrity,cells have evolved a complex DNA repair system to detect,signal and repair a diversity of DNA lesions.Homologous recombination(HR)-mediated DNA repair represents an error-free repair mechanism to maintain genomic integrity and ensure high-fidelity transmission of genetic information.Deficiencies in HR repair are of tremendous importance in the etiology of human cancers and at the same time offer great opportunities for designing targeted therapeutic strategies.The increase in the number of proteins identified as being involved in HR repair has dramatically shifted our concept of the proteins involved in this process:traditionally viewed as existing in a linear and simple pathway,today they are viewed as existing in a dynamic and interconnected network.Moreover,exploration of the targets within this network that can be modulated by small molecule drugs has led to the discovery of many effective kinase inhibitors,such as ATM,ATR,DNA-PK,CHK1,and CHK2 inhibitors.In preclinical studies,these inhibitors have been shown to sensitize cancer cells to chemotherapy and radiation therapy.The most exciting discovery in the field of HR repair is the identification of the synthetic lethality relationship between poly(ADPribose)polymerase(PARP)inhibitors and HR deficiency.The promises of clinical applications of PARP inhibitors and the concept of synthetic lethality also bring challenges into focus.Future research directions in the area of HR repair include determining how to identify the patients most likely to benefit from PARP inhibitors and developing strategies to overcome resistance to PARP inhibitors.展开更多
土壤有机碳(SOC)的组成和存在形态影响土壤碳库稳定性,揭示SOC组分构成及含量特征,对发挥土壤碳库功能具有重要意义。本研究以华南第一高峰-广西猫儿山为对象,采集不同海拔(460~2120 m)的土壤剖面发生层的土壤,分别测定基于化学组成、...土壤有机碳(SOC)的组成和存在形态影响土壤碳库稳定性,揭示SOC组分构成及含量特征,对发挥土壤碳库功能具有重要意义。本研究以华南第一高峰-广西猫儿山为对象,采集不同海拔(460~2120 m)的土壤剖面发生层的土壤,分别测定基于化学组成、密度和粒径区分的胡敏酸碳(HAC)、富里酸碳(FAC)和胡敏素碳(HC)、轻组有机碳(LFOC)和重组有机碳(HFOC)、颗粒有机碳(POC)和矿物结合态有机碳(MOC)含量,分析不同海拔SOC组分特征及其生态意义。结果表明:(1)土壤HAC、FAC、HC、LFOC、HFOC、POC、MOC含量分别为0.10~8.56 g kg^-1、0.33~25.62 g kg^-1、1.38~70.46 g kg^-1、0.01~41.94 g kg^-1、1.95~72.73 g kg^-1、0.41~21.37 g kg^-1、1.38~104.74 g kg^-1;(2)在海拔460~1400 m的常绿阔叶林植被下,土壤HC、HAC、FAC、POC、HFOC、MOC含量随海拔升高总体上呈增加趋势,而土壤LFOC含量随海拔升高总体上呈先增加后降低趋势;在海拔1400~1580 m的常绿落叶阔叶混交林植被下,土壤HAC、FAC含量随海拔升高保持平稳趋势,而HC、LFOC、POC、HFOC、MOC呈增加趋势;在海拔1580~2005 m的针阔混交林植被条件下,土壤HC、HAC、LFOC、POC、HFOC、MOC含量明显低于其相邻植被类型;在海拔2005~2120 m的山顶矮林和灌草丛植被下,HC、FAC、HAC、LFOC、HFOC、MOC含量均随海拔升高呈陡峭上升趋势,而POC呈略微的下降趋势;(3)HFOC/SOC和MOC/SOC均随土壤深度增加呈增大趋势,随海拔升高呈减小趋势,而LFOC/SOC和POC/SOC则与之相反;惰性态有机碳(MOC、HFOC)占SOC比例分别为63.44%~99.71%和68.41%~93.89%,是土壤有机碳的主要组成部分;(4)LFOC对海拔和土壤深度变化的平均敏感性指数均显著高于其他碳组分,能够敏感反映土壤碳库随海拔和土壤深度的变化。展开更多
文摘Genomic instability is a characteristic of cancer cells.In order to maintain genomic integrity,cells have evolved a complex DNA repair system to detect,signal and repair a diversity of DNA lesions.Homologous recombination(HR)-mediated DNA repair represents an error-free repair mechanism to maintain genomic integrity and ensure high-fidelity transmission of genetic information.Deficiencies in HR repair are of tremendous importance in the etiology of human cancers and at the same time offer great opportunities for designing targeted therapeutic strategies.The increase in the number of proteins identified as being involved in HR repair has dramatically shifted our concept of the proteins involved in this process:traditionally viewed as existing in a linear and simple pathway,today they are viewed as existing in a dynamic and interconnected network.Moreover,exploration of the targets within this network that can be modulated by small molecule drugs has led to the discovery of many effective kinase inhibitors,such as ATM,ATR,DNA-PK,CHK1,and CHK2 inhibitors.In preclinical studies,these inhibitors have been shown to sensitize cancer cells to chemotherapy and radiation therapy.The most exciting discovery in the field of HR repair is the identification of the synthetic lethality relationship between poly(ADPribose)polymerase(PARP)inhibitors and HR deficiency.The promises of clinical applications of PARP inhibitors and the concept of synthetic lethality also bring challenges into focus.Future research directions in the area of HR repair include determining how to identify the patients most likely to benefit from PARP inhibitors and developing strategies to overcome resistance to PARP inhibitors.
文摘土壤有机碳(SOC)的组成和存在形态影响土壤碳库稳定性,揭示SOC组分构成及含量特征,对发挥土壤碳库功能具有重要意义。本研究以华南第一高峰-广西猫儿山为对象,采集不同海拔(460~2120 m)的土壤剖面发生层的土壤,分别测定基于化学组成、密度和粒径区分的胡敏酸碳(HAC)、富里酸碳(FAC)和胡敏素碳(HC)、轻组有机碳(LFOC)和重组有机碳(HFOC)、颗粒有机碳(POC)和矿物结合态有机碳(MOC)含量,分析不同海拔SOC组分特征及其生态意义。结果表明:(1)土壤HAC、FAC、HC、LFOC、HFOC、POC、MOC含量分别为0.10~8.56 g kg^-1、0.33~25.62 g kg^-1、1.38~70.46 g kg^-1、0.01~41.94 g kg^-1、1.95~72.73 g kg^-1、0.41~21.37 g kg^-1、1.38~104.74 g kg^-1;(2)在海拔460~1400 m的常绿阔叶林植被下,土壤HC、HAC、FAC、POC、HFOC、MOC含量随海拔升高总体上呈增加趋势,而土壤LFOC含量随海拔升高总体上呈先增加后降低趋势;在海拔1400~1580 m的常绿落叶阔叶混交林植被下,土壤HAC、FAC含量随海拔升高保持平稳趋势,而HC、LFOC、POC、HFOC、MOC呈增加趋势;在海拔1580~2005 m的针阔混交林植被条件下,土壤HC、HAC、LFOC、POC、HFOC、MOC含量明显低于其相邻植被类型;在海拔2005~2120 m的山顶矮林和灌草丛植被下,HC、FAC、HAC、LFOC、HFOC、MOC含量均随海拔升高呈陡峭上升趋势,而POC呈略微的下降趋势;(3)HFOC/SOC和MOC/SOC均随土壤深度增加呈增大趋势,随海拔升高呈减小趋势,而LFOC/SOC和POC/SOC则与之相反;惰性态有机碳(MOC、HFOC)占SOC比例分别为63.44%~99.71%和68.41%~93.89%,是土壤有机碳的主要组成部分;(4)LFOC对海拔和土壤深度变化的平均敏感性指数均显著高于其他碳组分,能够敏感反映土壤碳库随海拔和土壤深度的变化。
