The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform

Abdelhafid Bendahmane - One of the best experts on this subject based on the ideXlab platform.

  • a transposon induced Epigenetic Change leads to sex determination in melon
    Nature, 2009
    Co-Authors: Antoine Martin, Christelle Troadec, Adnane Boualem, Mazen Rajab, Ronan Fernandez, Halima Morin, Michel Pitrat, Catherine Dogimont, Abdelhafid Bendahmane
    Abstract:

    Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem. This mechanism results in the enhancement of outcrossing and promotes genetic variability, the consequences of which are advantageous to the evolution of a species. In melon, sexual forms are controlled by identity of the alleles at the andromonoecious (a) and gynoecious (g) loci. We previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS-7, that represses stamen development in female flowers. Here we show that the transition from male to female flowers in gynoecious lines results from Epigenetic Changes in the promoter of a transcription factor, CmWIP1. This natural and heritable Epigenetic Change resulted from the insertion of a transposon, which is required for initiation and maintenance of the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. Moreover, we show that CmWIP1 indirectly represses the expression of the andromonoecious gene, CmACS-7, to allow stamen development. Together our data indicate a model in which CmACS-7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon.

  • A transposon-induced Epigenetic Change leads to sex determination in melon
    Nature, 2009
    Co-Authors: Antoine Martin, Christelle Troadec, Adnane Boualem, Mazen Rajab, Ronan Fernandez, Halima Morin, Michel Pitrat, Catherine Dogimont, Abdelhafid Bendahmane
    Abstract:

    During the development of flowering plants, sex determination leads to the physical separation of male and female flowers from an originally bisexual floral meristem. Here, in melon, the transition from male to female flowers is shown to result from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . These Epigenetic Changes are caused by insertion of a neighbouring transposon, which is required for initiation and maintenance of DNA methylation that spreads to the CmWIP1 promoter resulting in silencing of the gene. A model for the development of male, female and hermaphrodite flowers is proposed. During the development of flowering plants, sex determination leads to the physical separation of male and female flowers from an originally bisexual floral meristem. Here, in melon, the transition from male to female flowers is shown to result from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . The data presented are used to propose a model for the control and development of male, female and hermaphrodite flowers in melon. Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem^ 1 , 2 . This mechanism results in the enhancement of outcrossing and promotes genetic variability, the consequences of which are advantageous to the evolution of a species^ 3 . In melon, sexual forms are controlled by identity of the alleles at the andromonoecious ( a ) and gynoecious ( g ) loci^ 4 . We previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS-7, that represses stamen development in female flowers^ 5 . Here we show that the transition from male to female flowers in gynoecious lines results from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . This natural and heritable Epigenetic Change resulted from the insertion of a transposon, which is required for initiation and maintenance of the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. Moreover, we show that CmWIP1 indirectly represses the expression of the andromonoecious gene, CmACS-7 , to allow stamen development. Together our data indicate a model in which CmACS-7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon.

Chen-hsiang Yeang - One of the best experts on this subject based on the ideXlab platform.

  • impact of genetic dynamics and single cell heterogeneity on development of nonstandard personalized medicine strategies for cancer
    Proceedings of the National Academy of Sciences of the United States of America, 2012
    Co-Authors: Gunter S Schemmann, Chen-hsiang Yeang, Robert A. Beckman
    Abstract:

    Cancers are heterogeneous and genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type. However, it does not yet systematically address heterogeneity at the single-cell level within a single individual’s cancer or the dynamic nature of cancer due to genetic and Epigenetic Change as well as transient functional Changes. We have developed a mathematical model of personalized cancer therapy incorporating genetic evolutionary dynamics and single-cell heterogeneity, and have examined simulated clinical outcomes. Analyses of an illustrative case and a virtual clinical trial of over 3 million evaluable “patients” demonstrate that augmented (and sometimes counterintuitive) nonstandard personalized medicine strategies may lead to superior patient outcomes compared with the current personalized medicine approach. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression, generally focusing on the average, static, and current properties of the sample. Nonstandard strategies also consider minor subclones, dynamics, and predicted future tumor states. Our methods allow systematic study and evaluation of nonstandard personalized medicine strategies. These findings may, in turn, suggest global adjustments and enhancements to translational oncology research paradigms.

  • Abstract LB-448: Next generation personalized medicine strategies incorporating genetic dynamics and single cell heterogeneity may lead to improved outcomes
    Cancer Research, 2012
    Co-Authors: Robert A. Beckman, Gunter S Schemmann, Chen-hsiang Yeang
    Abstract:

    Introduction: Cancers are heterogeneous and often genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type occurring within different individuals. However, it does not yet address heterogeneity at the single cell level within individual cancers or the dynamic nature of cancer, due to heritable genetic and Epigenetic Change, as well as transient functional Changes. We established methods for evaluating personalized medicine strategies, and compared the current personalized medicine strategy to alternatives. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression. This strategy focuses on the average, static, and current properties of the sample. Next-generation strategies also consider minor sub-clones, dynamics, and predicted future tumor states. Methods: We developed a mathematical model of targeted cancer therapy incorporating genetic evolutionary dynamics and single cell heterogeneity, and examined simulated clinical outcomes (cell numbers of clones and sub-clones, projected survival). We compared the current personalized medicine strategy to 5 alternative personalized strategies. The latter strategies explicitly considered sub-clones, evolutionary dynamics, and likely future sub-clones in addition to the current predominant clone. Particular emphasis was given to the prevention of incurable, multiply resistant sub-clones. Results: We carried out a computerized virtual clinical trial of over 3 million evaluable cancer “patients,” comparing current personalized medicine and 5 alternative strategies. While the current personalized medicine strategy was equally effective to the alternatives in 2/3 of the cases, in 1/3 of the cases alternative strategies led to improved outcomes. All alternatives tested resulted in an approximate doubling in mean and median survival compared to current personalized medicine and an increase in the apparent cure rate from 0.7% for current personalized medicine to 17-20% for alternatives. In no case was the current personalized medicine strategy superior. Conclusions: These findings may lead to improved patient outcomes. Further, they suggest global enhancements to translational oncology research paradigms: for example, molecular characterization of incurable, multiply resistant “end states” from autopsy may be equally or more important than characterizing initial diagnostic states. We have developed methods to evaluate alternative personalized medicine strategies. Next generation strategies may consider sub-clones, evolutionary dynamics, and predicted future states. Application of knowledge from growing molecular and empirical oncology databases may allow more informative therapeutic simulations than previously possible. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-448. doi:1538-7445.AM2012-LB-448

Kazuaki Kawai - One of the best experts on this subject based on the ideXlab platform.

  • Causes and prevention of occupational cancer
    Journal of UOEH, 2013
    Co-Authors: Kazuaki Kawai
    Abstract:

    : Cancer is the leading cause of death in Japan, and is responsible for 30 % of all deaths. Among these deaths, the contributing rate of occupational cancer is only a few percent. However, it is a serious problem for workers exposed to certain carcinogens within the workplace, because they are subjected to high levels of carcinogens throughout their workday. The early adverse health effects exerted by carcinogens are closely related to carcinogenesis. As biomarkers for cancer prevention, 8-hydroxydeoxyguanosine, as an oxidative stress marker, DNA adducts, and cytosine C-5 methylation, as a marker of Epigenetic Change, may be useful to monitor.

  • dna methylation at the c 5 position of cytosine by a methyl radical a link between environmental agents and Epigenetic Change
    Genes and Environment, 2011
    Co-Authors: Hiroshi Kasai, Kazuaki Kawai, Yunshan Li
    Abstract:

    Methylation of the cytosine C-5 position in the promoter region of tumor suppressor genes is an important mechanism of carcinogenesis in addition to gene mutation. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred in the monomer nucleoside and DNA by various methyl radical generating systems, including environmental agents. The possible role of this radical-induced DNA methylation in carcinogenesis is discussed in connection with the presently accepted concept of cancer Epigenetics.

  • dna methylation at the c 5 position of cytosine by methyl radicals a possible role for Epigenetic Change during carcinogenesis by environmental agents
    Chemical Research in Toxicology, 2009
    Co-Authors: Hiroshi Kasai, Kazuaki Kawai
    Abstract:

    During carcinogenesis, methylation of the C-5 position of cytosines in the promoter region of tumor suppressor genes is often observed. Enzymatic DNA methylation is a widely accepted mechanism for this phenomenon. It is interesting to propose a free radical mechanism for 5-methyldeoxycytidine (m5dC) production, because the C-5 position of cytosine is an active site for free radical reactions. When deoxycytidine (dC) and cumene hydroperoxide (CuOOH), a tumor promoter and a methyl radical producer, were reacted in the presence of ferrous ion at pH 7.4, the formation of m5dC was observed. The same reaction also proceeded with t-butyl hydroperoxide (BuOOH). The formation of m5dC was also observed in DNA by the CuOOH treatment. This is the first report of chemical DNA methylation at cytosine C-5 by environmental tumor promoters. We propose here that this reaction is one of the important mechanisms of de novo DNA methylation during carcinogenesis, because methyl radicals are produced by the biotransformation of...

Robert A. Beckman - One of the best experts on this subject based on the ideXlab platform.

  • impact of genetic dynamics and single cell heterogeneity on development of nonstandard personalized medicine strategies for cancer
    Proceedings of the National Academy of Sciences of the United States of America, 2012
    Co-Authors: Gunter S Schemmann, Chen-hsiang Yeang, Robert A. Beckman
    Abstract:

    Cancers are heterogeneous and genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type. However, it does not yet systematically address heterogeneity at the single-cell level within a single individual’s cancer or the dynamic nature of cancer due to genetic and Epigenetic Change as well as transient functional Changes. We have developed a mathematical model of personalized cancer therapy incorporating genetic evolutionary dynamics and single-cell heterogeneity, and have examined simulated clinical outcomes. Analyses of an illustrative case and a virtual clinical trial of over 3 million evaluable “patients” demonstrate that augmented (and sometimes counterintuitive) nonstandard personalized medicine strategies may lead to superior patient outcomes compared with the current personalized medicine approach. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression, generally focusing on the average, static, and current properties of the sample. Nonstandard strategies also consider minor subclones, dynamics, and predicted future tumor states. Our methods allow systematic study and evaluation of nonstandard personalized medicine strategies. These findings may, in turn, suggest global adjustments and enhancements to translational oncology research paradigms.

  • Abstract LB-448: Next generation personalized medicine strategies incorporating genetic dynamics and single cell heterogeneity may lead to improved outcomes
    Cancer Research, 2012
    Co-Authors: Robert A. Beckman, Gunter S Schemmann, Chen-hsiang Yeang
    Abstract:

    Introduction: Cancers are heterogeneous and often genetically unstable. Current practice of personalized medicine tailors therapy to heterogeneity between cancers of the same organ type occurring within different individuals. However, it does not yet address heterogeneity at the single cell level within individual cancers or the dynamic nature of cancer, due to heritable genetic and Epigenetic Change, as well as transient functional Changes. We established methods for evaluating personalized medicine strategies, and compared the current personalized medicine strategy to alternatives. Current personalized medicine matches therapy to a tumor molecular profile at diagnosis and at tumor relapse or progression. This strategy focuses on the average, static, and current properties of the sample. Next-generation strategies also consider minor sub-clones, dynamics, and predicted future tumor states. Methods: We developed a mathematical model of targeted cancer therapy incorporating genetic evolutionary dynamics and single cell heterogeneity, and examined simulated clinical outcomes (cell numbers of clones and sub-clones, projected survival). We compared the current personalized medicine strategy to 5 alternative personalized strategies. The latter strategies explicitly considered sub-clones, evolutionary dynamics, and likely future sub-clones in addition to the current predominant clone. Particular emphasis was given to the prevention of incurable, multiply resistant sub-clones. Results: We carried out a computerized virtual clinical trial of over 3 million evaluable cancer “patients,” comparing current personalized medicine and 5 alternative strategies. While the current personalized medicine strategy was equally effective to the alternatives in 2/3 of the cases, in 1/3 of the cases alternative strategies led to improved outcomes. All alternatives tested resulted in an approximate doubling in mean and median survival compared to current personalized medicine and an increase in the apparent cure rate from 0.7% for current personalized medicine to 17-20% for alternatives. In no case was the current personalized medicine strategy superior. Conclusions: These findings may lead to improved patient outcomes. Further, they suggest global enhancements to translational oncology research paradigms: for example, molecular characterization of incurable, multiply resistant “end states” from autopsy may be equally or more important than characterizing initial diagnostic states. We have developed methods to evaluate alternative personalized medicine strategies. Next generation strategies may consider sub-clones, evolutionary dynamics, and predicted future states. Application of knowledge from growing molecular and empirical oncology databases may allow more informative therapeutic simulations than previously possible. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-448. doi:1538-7445.AM2012-LB-448

Antoine Martin - One of the best experts on this subject based on the ideXlab platform.

  • a transposon induced Epigenetic Change leads to sex determination in melon
    Nature, 2009
    Co-Authors: Antoine Martin, Christelle Troadec, Adnane Boualem, Mazen Rajab, Ronan Fernandez, Halima Morin, Michel Pitrat, Catherine Dogimont, Abdelhafid Bendahmane
    Abstract:

    Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem. This mechanism results in the enhancement of outcrossing and promotes genetic variability, the consequences of which are advantageous to the evolution of a species. In melon, sexual forms are controlled by identity of the alleles at the andromonoecious (a) and gynoecious (g) loci. We previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS-7, that represses stamen development in female flowers. Here we show that the transition from male to female flowers in gynoecious lines results from Epigenetic Changes in the promoter of a transcription factor, CmWIP1. This natural and heritable Epigenetic Change resulted from the insertion of a transposon, which is required for initiation and maintenance of the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. Moreover, we show that CmWIP1 indirectly represses the expression of the andromonoecious gene, CmACS-7, to allow stamen development. Together our data indicate a model in which CmACS-7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon.

  • A transposon-induced Epigenetic Change leads to sex determination in melon
    Nature, 2009
    Co-Authors: Antoine Martin, Christelle Troadec, Adnane Boualem, Mazen Rajab, Ronan Fernandez, Halima Morin, Michel Pitrat, Catherine Dogimont, Abdelhafid Bendahmane
    Abstract:

    During the development of flowering plants, sex determination leads to the physical separation of male and female flowers from an originally bisexual floral meristem. Here, in melon, the transition from male to female flowers is shown to result from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . These Epigenetic Changes are caused by insertion of a neighbouring transposon, which is required for initiation and maintenance of DNA methylation that spreads to the CmWIP1 promoter resulting in silencing of the gene. A model for the development of male, female and hermaphrodite flowers is proposed. During the development of flowering plants, sex determination leads to the physical separation of male and female flowers from an originally bisexual floral meristem. Here, in melon, the transition from male to female flowers is shown to result from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . The data presented are used to propose a model for the control and development of male, female and hermaphrodite flowers in melon. Sex determination in plants leads to the development of unisexual flowers from an originally bisexual floral meristem^ 1 , 2 . This mechanism results in the enhancement of outcrossing and promotes genetic variability, the consequences of which are advantageous to the evolution of a species^ 3 . In melon, sexual forms are controlled by identity of the alleles at the andromonoecious ( a ) and gynoecious ( g ) loci^ 4 . We previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS-7, that represses stamen development in female flowers^ 5 . Here we show that the transition from male to female flowers in gynoecious lines results from Epigenetic Changes in the promoter of a transcription factor, CmWIP1 . This natural and heritable Epigenetic Change resulted from the insertion of a transposon, which is required for initiation and maintenance of the spreading of DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting in the development of unisexual male flowers. Moreover, we show that CmWIP1 indirectly represses the expression of the andromonoecious gene, CmACS-7 , to allow stamen development. Together our data indicate a model in which CmACS-7 and CmWIP1 interact to control the development of male, female and hermaphrodite flowers in melon.