Water status is one of the critical factors affecting rice production. Rice cultivars tolerant to drought stress at the vegetative stage under field conditions were selected. Seven rice cultivars, namely, KDML 105, IR...Water status is one of the critical factors affecting rice production. Rice cultivars tolerant to drought stress at the vegetative stage under field conditions were selected. Seven rice cultivars, namely, KDML 105, IR58821, CT9993, IR62266, IR57514, IR52561 and BT, were included in this study. The plant height, number of tillers per plant, leaf rolling, leaf death, leaf water potential, relative leaf water content and proline content in plants subjected to drought stress for 0, 20 and 60 days were recorded. Based upon the levels of water stress tolerance, three groups of rice cultivars were recognized, as follows: highly drought-tolerant, moderately drought-tolerant and drought-sensitive cultivars. The CT9993 rice cultivar was considered to be a highly drought-tolerant cultivar. The moderately drought-tolerant cultivars included KDML 105, IR58821, IR57514, IR52561 and BT. The IR62266 cultivar was considered sensitive to drought.展开更多
AIM:To investigate the proteome changes of stem cells due to ciclopirox olamine (CPX) treatment compared to control and retinoic acid treated cells. METHODS:Stem cells (SCs) are cells, which have the ability to contin...AIM:To investigate the proteome changes of stem cells due to ciclopirox olamine (CPX) treatment compared to control and retinoic acid treated cells. METHODS:Stem cells (SCs) are cells, which have the ability to continuously divide and differentiate into various other kinds of cells. Murine embryonic stem cells (ESCs) and multipotent adult germline stem cells (maG-SCs) were treated with CPX, which has been shown to have an antiproliferative effect on stem cells, and compared to stem cells treated with retinoic acid (RA),which is known to have a differentiating effect on stem cells. Classical proteomic techniques like 2-D gel electrophoresis and differential in-gel electrophoresis (DIGE) were used to generate 2D protein maps from stem cells treated with RA or CPX as well as from non-treated stem cells. The resulting 2D gels were scanned and the digitalized images were collated with the help of Delta 2D software. The differentially expressed proteins were analyzed by a MALDI-TOF-TOF mass spectrometer, and the identified proteins were investigated and categorized using bioinformatics. RESULTS:Treatment of stem cells with CPX, a synthetic antifungal clinically used to treat superficial mycoses, resulted in an antiproliferative effect in vitro, without impairment of pluripotency. To understand the mechanisms induced by CPX treatments which results in arrest of cell cycle without any marked effect on pluripotency, a comparative proteomics study was conducted. The obtained data revealed that the CPX impact on cell proliferation was accompanied with a significant alteration in stem cell proteome. By peptide mass fingerprinting and tandem mass spectrometry combined with searches of protein sequence databases, a set of 316 proteins was identified, corresponding to a library of 125 non-redundant proteins. With proteomic analysis of ESCs and maGSCs treated with CPX and RA, we could identify more than 90 single proteins, which were differently expressed in both cell lines. We could highlight, that CPX treatment of stem cells, with subsequent proliferation inhibition, resulted in an alteration of the expression of 56 proteins compared to nontreated cells, and 54 proteins compared to RA treated cells. Bioinformatics analysis of the regulated proteins demonstrated their involvement in various biological processes. To our interest, a number of proteins have potential roles in the regulation of cell proliferation either directly or indirectly. Furthermore the classification of the altered polypeptides according to their main known/postulated functions revealed that the majority of these proteins are involved in molecular functions like nucleotide binding and metal ion binding, and biological processes like nucleotide biosynthetic processes, gene expression, embryonic development, regulation of transcription, cell cycle processes, RNA and mRNA processing. Proteins, which are involved in nucleotide biosynthetic process and proteolysis, were downregulated in CPX treated cells compared to control, as well as in RA treated cells, which may explain the cell cycle arrest. Moreover, proteins which were involved in cell death, positive regulation of biosynthetic process, response to organic substance, glycolysis, anti-apoptosis, and phosphorylation were downregulated in RA treated cells compared to control and CPX treated cells. CONCLUSION:The CPX treatment of SCs results in downregulation of nucleotide binding proteins and leads to cell cycle stop without impairment of pluripotency.展开更多
Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand ...Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic levels.These data were complemented with transcriptomics analysis for 39 cases.Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and MLLGB.MLLGA presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples.MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other cases.Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB.The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to treatment.In summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia.These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.展开更多
Dear Editor,Of all human tumors,pheochromocytomas and paragangliomas(PPGLs)have the highest heritability rate.Over 15%of PPGLs harbor mutations in genes encoding tricarboxylic acid(TCA)cycle-related enzymes that cause...Dear Editor,Of all human tumors,pheochromocytomas and paragangliomas(PPGLs)have the highest heritability rate.Over 15%of PPGLs harbor mutations in genes encoding tricarboxylic acid(TCA)cycle-related enzymes that cause oncometabolite accumulation and drive tumorigenesis via metabolic adaptation to hypoxia and global hypermethylation[1].The dihydrolipoamide S-succinyltransferase(DLST)gene was recently described as a new PPGL susceptibility gene[2].展开更多
文摘Water status is one of the critical factors affecting rice production. Rice cultivars tolerant to drought stress at the vegetative stage under field conditions were selected. Seven rice cultivars, namely, KDML 105, IR58821, CT9993, IR62266, IR57514, IR52561 and BT, were included in this study. The plant height, number of tillers per plant, leaf rolling, leaf death, leaf water potential, relative leaf water content and proline content in plants subjected to drought stress for 0, 20 and 60 days were recorded. Based upon the levels of water stress tolerance, three groups of rice cultivars were recognized, as follows: highly drought-tolerant, moderately drought-tolerant and drought-sensitive cultivars. The CT9993 rice cultivar was considered to be a highly drought-tolerant cultivar. The moderately drought-tolerant cultivars included KDML 105, IR58821, IR57514, IR52561 and BT. The IR62266 cultivar was considered sensitive to drought.
文摘AIM:To investigate the proteome changes of stem cells due to ciclopirox olamine (CPX) treatment compared to control and retinoic acid treated cells. METHODS:Stem cells (SCs) are cells, which have the ability to continuously divide and differentiate into various other kinds of cells. Murine embryonic stem cells (ESCs) and multipotent adult germline stem cells (maG-SCs) were treated with CPX, which has been shown to have an antiproliferative effect on stem cells, and compared to stem cells treated with retinoic acid (RA),which is known to have a differentiating effect on stem cells. Classical proteomic techniques like 2-D gel electrophoresis and differential in-gel electrophoresis (DIGE) were used to generate 2D protein maps from stem cells treated with RA or CPX as well as from non-treated stem cells. The resulting 2D gels were scanned and the digitalized images were collated with the help of Delta 2D software. The differentially expressed proteins were analyzed by a MALDI-TOF-TOF mass spectrometer, and the identified proteins were investigated and categorized using bioinformatics. RESULTS:Treatment of stem cells with CPX, a synthetic antifungal clinically used to treat superficial mycoses, resulted in an antiproliferative effect in vitro, without impairment of pluripotency. To understand the mechanisms induced by CPX treatments which results in arrest of cell cycle without any marked effect on pluripotency, a comparative proteomics study was conducted. The obtained data revealed that the CPX impact on cell proliferation was accompanied with a significant alteration in stem cell proteome. By peptide mass fingerprinting and tandem mass spectrometry combined with searches of protein sequence databases, a set of 316 proteins was identified, corresponding to a library of 125 non-redundant proteins. With proteomic analysis of ESCs and maGSCs treated with CPX and RA, we could identify more than 90 single proteins, which were differently expressed in both cell lines. We could highlight, that CPX treatment of stem cells, with subsequent proliferation inhibition, resulted in an alteration of the expression of 56 proteins compared to nontreated cells, and 54 proteins compared to RA treated cells. Bioinformatics analysis of the regulated proteins demonstrated their involvement in various biological processes. To our interest, a number of proteins have potential roles in the regulation of cell proliferation either directly or indirectly. Furthermore the classification of the altered polypeptides according to their main known/postulated functions revealed that the majority of these proteins are involved in molecular functions like nucleotide binding and metal ion binding, and biological processes like nucleotide biosynthetic processes, gene expression, embryonic development, regulation of transcription, cell cycle processes, RNA and mRNA processing. Proteins, which are involved in nucleotide biosynthetic process and proteolysis, were downregulated in CPX treated cells compared to control, as well as in RA treated cells, which may explain the cell cycle arrest. Moreover, proteins which were involved in cell death, positive regulation of biosynthetic process, response to organic substance, glycolysis, anti-apoptosis, and phosphorylation were downregulated in RA treated cells compared to control and CPX treated cells. CONCLUSION:The CPX treatment of SCs results in downregulation of nucleotide binding proteins and leads to cell cycle stop without impairment of pluripotency.
基金We thank Adrian Kontor for technical help with the manipulation of AML primary samples,Sarah Mueller for managing the supply of AML primary samples,Janet Matthews for assisting with the processing of patient clinical data,Ruth Osuntola for technical assistance with the mass spectrometry experiments and the FIMM High Throughput Biomedicine Unit for their expert technical support.This work was mainly funded by Cancer Research UK(C15966/A24375)with additional contribution from Blood Cancer UK(20008).All authors have read and approved the article.
文摘Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse prognosis.For these patients,targeted therapies have not yet made a significant clinical impact.To understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic levels.These data were complemented with transcriptomics analysis for 39 cases.Data integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and MLLGB.MLLGA presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples.MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other cases.Intermediate-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to MLLGB.The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to treatment.In summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia.These data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.
基金supported by the Instituto de Salud CarlosⅢ(ISCⅢ)through the“Acción Estratégica en Salud”(AES)(projects PI18/00454 and PI22/01490 to A.C.and PI20/01169 to M.R.)cofounded by the European Regional Development Fund(ERDF)+1 种基金supported by the Spanish Ministry of Science,Innovation and Universities“Formación del Profesorado Universitario-FPU”fellowship with ID number FPU19/04940supported by‘la Caixa’Foundation(ID 100010434)under agreement LCF/BQ/PI20/11760011.
文摘Dear Editor,Of all human tumors,pheochromocytomas and paragangliomas(PPGLs)have the highest heritability rate.Over 15%of PPGLs harbor mutations in genes encoding tricarboxylic acid(TCA)cycle-related enzymes that cause oncometabolite accumulation and drive tumorigenesis via metabolic adaptation to hypoxia and global hypermethylation[1].The dihydrolipoamide S-succinyltransferase(DLST)gene was recently described as a new PPGL susceptibility gene[2].
