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
Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone mar...Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).展开更多
The ecosystem of the Three Gorges in the Yangtze River was changed into an artificial lake(reservoir)ecosystem after impoundment in June 2003.We surveyed the seasonal variation and spatial distribution of copepods fro...The ecosystem of the Three Gorges in the Yangtze River was changed into an artificial lake(reservoir)ecosystem after impoundment in June 2003.We surveyed the seasonal variation and spatial distribution of copepods from April 2004 to January 2005 in order to provide data for clarifying the successional pattern of the ecosystem.From Jiangjin to Maoping,eight copepod species were collected and classified into Calanoida(2),Harpacticoida(1),and Cyclopoida(5).Among them,Mesocyclops pehpeiensis,M.leuckarti and Sinocalanus dorrii had a relatively wide distribution.No distinct difference in species number was found among the sampling sites,but the species composition was different.Species composition,distribution and density of copepods showed significant seasonal variations.In addition,copepod density showed an obvious gradient with the distance from the reservoir dam:the nearer to the dam,the denser the copepods.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supported by grants from the Innovative Clinical Technique of Guangzhou,China(No.2019GX04 and 2023C-GX01 to YPZ and SQW,respectively)2019 Annual Research Project of The China Marrow Donor Program(No.CMDP201902 to SQW)+1 种基金Guangzhou Municipal Science and Technology project(China)(No.202002030035 to SQW)the Natural Science Foundation of Guangdong Province,China(No.2018A0303130179 to MZ).
文摘Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).
文摘The ecosystem of the Three Gorges in the Yangtze River was changed into an artificial lake(reservoir)ecosystem after impoundment in June 2003.We surveyed the seasonal variation and spatial distribution of copepods from April 2004 to January 2005 in order to provide data for clarifying the successional pattern of the ecosystem.From Jiangjin to Maoping,eight copepod species were collected and classified into Calanoida(2),Harpacticoida(1),and Cyclopoida(5).Among them,Mesocyclops pehpeiensis,M.leuckarti and Sinocalanus dorrii had a relatively wide distribution.No distinct difference in species number was found among the sampling sites,but the species composition was different.Species composition,distribution and density of copepods showed significant seasonal variations.In addition,copepod density showed an obvious gradient with the distance from the reservoir dam:the nearer to the dam,the denser the copepods.
