The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Gábor E. Tusnády - One of the best experts on this subject based on the ideXlab platform.
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T cells survey the stability of the self: a Testable Hypothesis on the homeostatic role of TCR-MHC interactions.
International archives of allergy and immunology, 2007Co-Authors: Tibor Bakács, Jitendra N. Mehrishi, Tamás Szabados, László Varga, Miklós Szabó, Gábor E. TusnádyAbstract:In the lifetime of an individual, every single gene will have undergone mutation on about 10(10) separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesize that the evolutionary pressure driving the creation of the T cell receptor (TCR) repertoire was primarily the homeostatic surveillance of the genome. The subtly variable T cells may in fact constitute an evolutionary link between the invariable innate and hypervariable B cell systems. The new model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected TCR and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. Notwithstanding, the 'homeostatic role of T cells' model offers a more realistic explanation as to how a naïve clonal immune system can cope with the much faster replicating pathogens, despite a limited repertoire that is capable of facing only a small fraction of the vast antigenic universe at a time.
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t cells survey the stability of the self a Testable Hypothesis on the homeostatic role of tcr mhc interactions
International Archives of Allergy and Immunology, 2007Co-Authors: Tibor Bakács, Jitendra N. Mehrishi, Tamás Szabados, László Varga, Miklós Szabó, Gábor E. TusnádyAbstract:In the lifetime of an individual, every single gene will have undergone mutation on about 1010 separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesiz
Anagha Joshi - One of the best experts on this subject based on the ideXlab platform.
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Insights into mammalian transcription control by systematic analysis of ChIP sequencing data
BMC Bioinformatics, 2018Co-Authors: Guillaume Devailly, Anagha JoshiAbstract:Background Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project. Results A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites are more cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease. Conclusion In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel Testable Hypothesis using this public resource.
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Insights into mammalian transcription control by systematic analysis of ChIP sequencing data
BMC Bioinformatics, 2018Co-Authors: Guillaume Devailly, Anagha JoshiAbstract:Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project. A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites aremore cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease. In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel Testable Hypothesis using this public resource.
Tibor Bakács - One of the best experts on this subject based on the ideXlab platform.
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T cells survey the stability of the self: a Testable Hypothesis on the homeostatic role of TCR-MHC interactions.
International archives of allergy and immunology, 2007Co-Authors: Tibor Bakács, Jitendra N. Mehrishi, Tamás Szabados, László Varga, Miklós Szabó, Gábor E. TusnádyAbstract:In the lifetime of an individual, every single gene will have undergone mutation on about 10(10) separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesize that the evolutionary pressure driving the creation of the T cell receptor (TCR) repertoire was primarily the homeostatic surveillance of the genome. The subtly variable T cells may in fact constitute an evolutionary link between the invariable innate and hypervariable B cell systems. The new model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected TCR and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. Notwithstanding, the 'homeostatic role of T cells' model offers a more realistic explanation as to how a naïve clonal immune system can cope with the much faster replicating pathogens, despite a limited repertoire that is capable of facing only a small fraction of the vast antigenic universe at a time.
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t cells survey the stability of the self a Testable Hypothesis on the homeostatic role of tcr mhc interactions
International Archives of Allergy and Immunology, 2007Co-Authors: Tibor Bakács, Jitendra N. Mehrishi, Tamás Szabados, László Varga, Miklós Szabó, Gábor E. TusnádyAbstract:In the lifetime of an individual, every single gene will have undergone mutation on about 1010 separate occasions. Nevertheless, cancer occurs mainly with advancing age. Here, we hypothesiz
Guillaume Devailly - One of the best experts on this subject based on the ideXlab platform.
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Insights into mammalian transcription control by systematic analysis of ChIP sequencing data
BMC Bioinformatics, 2018Co-Authors: Guillaume Devailly, Anagha JoshiAbstract:Background Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project. Results A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites are more cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease. Conclusion In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel Testable Hypothesis using this public resource.
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Insights into mammalian transcription control by systematic analysis of ChIP sequencing data
BMC Bioinformatics, 2018Co-Authors: Guillaume Devailly, Anagha JoshiAbstract:Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project. A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites aremore cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease. In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel Testable Hypothesis using this public resource.
Duane D. Dunkerson - One of the best experts on this subject based on the ideXlab platform.
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Malnutrition, urocanic acid, and sun may interact to suppress immunity in sojourners to high altitude.
Aviation Space and Environmental Medicine, 2001Co-Authors: John K. Hunter, Duane D. DunkersonAbstract:Irradiation of skin by ultraviolet radiation in mice and humans leads to a suppression of cell-mediated immunity. This process is initiated when one of the photoreceptors in skin, trans-urocanic acid, is photoisomerized to cis-urocanic acid, an immunomodulator. High levels of L-histidine, histamine, and trans-urocanic acid are found in humans and animals when they are protein malnourished. Mice fed on an elevated L-histidine diet have more trans-urocanic acid in the skin and are more susceptible to UV-induced immune suppression. Sojourners to high altitudes are malnourished, suffer protein catabolism, are exposed to sun, and often acquire infectious diseases. There is evidence that sunscreens may not adequately protect the immune system. Furthermore, UV intensity increases with altitude. We propose a Testable Hypothesis: UV radiation causes photoimmune suppression in sojourners to high altitude and this allows infectious diseases to develop. The mechanism we propose includes protein malnutrition, high levels of trans-urocanic acid, ultraviolet radiation, formation of cis-urocanic acid, immune suppression, and infection.
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The potential role for urocanic acid and sunlight in the immune suppression associated with protein malnutrition
Journal of Photochemistry and Photobiology B-biology, 1998Co-Authors: John K. Hunter, Duane D. DunkersonAbstract:Abstract Irradiation of skin by sunlight or ultraviolet B (UVB, 290–320 nm) brings about a downregulation of cell-mediated immunity. An action spectrum for photoimmune suppression in mice indicates that trans -urocanic acid absorbs UV photons and is isomerized to the cis -isomer in the stratum corneum. Cis -urocanic acid is subsequently shown to suppress cellular immunity in mice. When histidine is elevated in a mouse diet, a higher level of urocanic acid is detected in mouse skin. These mice are more susceptible to photoimmune suppression. There is evidence that humans and animals experiencing protein malnutrition have very high levels of urocanic acid and/or histidine. Urocanic acid is formed by deamination of histidine in one enzymatic step. We discuss the protein malnutrition of kwashiorkor patients. They experience suppressed immunity and disturbed histidine metabolism. Here, we present a Testable Hypothesis: one cause of the immune deficiency observed in humans with protein malnutrition is the photoconversion by UVB of increased levels of trans -urocanic acid in skin to cis -urocanic acid, which suppresses the cellular immune system.
