Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of ...Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive characterization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottomup MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of topdown and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.展开更多
Ecological restoration policies and their implementation are influenced by ecological and socioeconomic drivers.Top-down approach-based spatial planning,emphasizing hierarchical control within government structures,an...Ecological restoration policies and their implementation are influenced by ecological and socioeconomic drivers.Top-down approach-based spatial planning,emphasizing hierarchical control within government structures,and without a comprehensive consideration of social–ecological interactions may result in implementation failure and low efficiency.Although many researchers have indicated the necessity to engage social–ecological interactions between stakeholders in effective planning processes,socioeconomic drivers of ecological restoration on a large scale are difficult to quantify because of data scarcity and knowledge limitations.Here,we established a new ecological restoration planning approach linking a social–ecological system framework to large-scale ecological restoration planning.The new spatial planning approach integrates bottom-up approaches targeting stakeholder interests and provides social considerations for stakeholder behavior analysis.Based on this approach,a meta-analysis is introduced to recognize key socioeconomic and social–ecological factors influencing large-scale ecological restoration implementation,and a stochastic model is constructed to analyze the impact of socioeconomic drivers on the behavior of authorities and participants on a large scale.We used the Yangtze River Basin-based Conversion of Cropland to Forest Program(CCFP),one of the largest payments for ecosystem service programs worldwide,to quantify the socioeconomic impacts of large-scale ecological restoration programs.Current CCFP planning without socioeconomic considerations failed to achieve large-scale program goals and showed low investment efficiency,with 19.71% of the implemented area reconverting to cropland after contract expiry.In contrast,spatial matching between planned and actual restoration increased from 61.55% to 81.86% when socioeconomic drivers were included.In addition,compared to that with the current CCFP implementation,the cost effectiveness of spatial planning with social considerations improved by 46.94%.Thus,spatial optimization planning that integrates both top-down and bottom-up approaches can result in more practical and effective ecological restoration than top-down approaches alone.Our new approach incorporates socioeconomic factors into large-scale ecological restoration planning with high practicality and efficiency.展开更多
基金supported in part by the National Natural Science Foundation of China(Grant Nos.:91953102 and 81872836)Natural Science Foundation of Guangdong Province,China(Grant Nos.:2019A1515011265 and 2022A1515010965)+1 种基金the Fundamental Research Funds for Sun Yat-sen University,China(Grant No.:19ykzd26)Open Project Funding of the State Key Laboratory of Crop Stress Adaptation and Improvement(Grant No.:2020KF05).Huilin Li would like to thank the Pearl River Talent Recruitment Program for support.
文摘Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive characterization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottomup MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of topdown and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.
基金the National Natural Science Foundation of China(41925005 and 72022014)the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0307)。
文摘Ecological restoration policies and their implementation are influenced by ecological and socioeconomic drivers.Top-down approach-based spatial planning,emphasizing hierarchical control within government structures,and without a comprehensive consideration of social–ecological interactions may result in implementation failure and low efficiency.Although many researchers have indicated the necessity to engage social–ecological interactions between stakeholders in effective planning processes,socioeconomic drivers of ecological restoration on a large scale are difficult to quantify because of data scarcity and knowledge limitations.Here,we established a new ecological restoration planning approach linking a social–ecological system framework to large-scale ecological restoration planning.The new spatial planning approach integrates bottom-up approaches targeting stakeholder interests and provides social considerations for stakeholder behavior analysis.Based on this approach,a meta-analysis is introduced to recognize key socioeconomic and social–ecological factors influencing large-scale ecological restoration implementation,and a stochastic model is constructed to analyze the impact of socioeconomic drivers on the behavior of authorities and participants on a large scale.We used the Yangtze River Basin-based Conversion of Cropland to Forest Program(CCFP),one of the largest payments for ecosystem service programs worldwide,to quantify the socioeconomic impacts of large-scale ecological restoration programs.Current CCFP planning without socioeconomic considerations failed to achieve large-scale program goals and showed low investment efficiency,with 19.71% of the implemented area reconverting to cropland after contract expiry.In contrast,spatial matching between planned and actual restoration increased from 61.55% to 81.86% when socioeconomic drivers were included.In addition,compared to that with the current CCFP implementation,the cost effectiveness of spatial planning with social considerations improved by 46.94%.Thus,spatial optimization planning that integrates both top-down and bottom-up approaches can result in more practical and effective ecological restoration than top-down approaches alone.Our new approach incorporates socioeconomic factors into large-scale ecological restoration planning with high practicality and efficiency.
