The Experts below are selected from a list of 102750 Experts worldwide ranked by ideXlab platform
Said Mouzeyar - One of the best experts on this subject based on the ideXlab platform.
-
Positional cloning of a candidate gene for resistance to the sunflower downy mildew, Plasmopara halstedii race 300.
TAG Theoretical and Applied Genetics, 2015Co-Authors: Jérôme Franchel, Mohamed-Fouad Bouzidi, Paul Nicolas, Felicity Vear, Gisèle Bronner, Said MouzeyarAbstract:The resistance of sunflower to Plasmopara halstedii is conferred by major resistance genes denoted Pl. Previous genetic studies indicated that the majority of these genes are clustered on linkage groups 8 and 13. The Pl6 locus is one of the main clusters to have been identified, and confers resistance to several P. halstedii races. In this study, a map-based cloning strategy was implemented using a large segregating F2 population to establish a fine physical map of this cluster. A marker derived from a bacterial artificial chromosome (BAC) clone was found to be very tightly linked to the gene conferring resistance to race 300, and the corresponding BAC clone was sequenced and annotated. It contains several putative genes including three toll-Interleukin Receptor-nucleotide binding site-leucine rich repeats (TIR-NBS-LRR) genes. However, only one TIR-NBS-LRR appeared to be expressed, and thus constitutes a candidate gene for resistance to P. halstedii race 300.
Matthew C P Smith - One of the best experts on this subject based on the ideXlab platform.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Nyall R London, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Matthew C P SmithAbstract:Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease. Cytokines, the circulating proteins that activate the immune system, also disrupt cell–cell junctions and can trigger tissue oedema and destruction. Using an in vitro human endothelial cell model, this study shows that the disruptive effects of one such cytokine, Interleukin-1 β, are NF-κB independent. Instead they depend on a novel non-canonical pathway involving intracellular GTPases that regulate cadherin trafficking and cell–cell interactions. Targeting of this signalling cascade in an animal model of arthritis prevents cytokine-mediated disruption of endothelial cell barriers and limits tissue damage. The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment1,2,3,4. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response5,6. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell–cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture7,8,9. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88–ARNO–ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Nyall London, Matthew C P SmithAbstract:The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
Jinping Guo - One of the best experts on this subject based on the ideXlab platform.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Nyall R London, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Matthew C P SmithAbstract:Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease. Cytokines, the circulating proteins that activate the immune system, also disrupt cell–cell junctions and can trigger tissue oedema and destruction. Using an in vitro human endothelial cell model, this study shows that the disruptive effects of one such cytokine, Interleukin-1 β, are NF-κB independent. Instead they depend on a novel non-canonical pathway involving intracellular GTPases that regulate cadherin trafficking and cell–cell interactions. Targeting of this signalling cascade in an animal model of arthritis prevents cytokine-mediated disruption of endothelial cell barriers and limits tissue damage. The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment1,2,3,4. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response5,6. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell–cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture7,8,9. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88–ARNO–ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Nyall London, Matthew C P SmithAbstract:The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
Jérôme Franchel - One of the best experts on this subject based on the ideXlab platform.
-
Positional cloning of a candidate gene for resistance to the sunflower downy mildew, Plasmopara halstedii race 300.
TAG Theoretical and Applied Genetics, 2015Co-Authors: Jérôme Franchel, Mohamed-Fouad Bouzidi, Paul Nicolas, Felicity Vear, Gisèle Bronner, Said MouzeyarAbstract:The resistance of sunflower to Plasmopara halstedii is conferred by major resistance genes denoted Pl. Previous genetic studies indicated that the majority of these genes are clustered on linkage groups 8 and 13. The Pl6 locus is one of the main clusters to have been identified, and confers resistance to several P. halstedii races. In this study, a map-based cloning strategy was implemented using a large segregating F2 population to establish a fine physical map of this cluster. A marker derived from a bacterial artificial chromosome (BAC) clone was found to be very tightly linked to the gene conferring resistance to race 300, and the corresponding BAC clone was sequenced and annotated. It contains several putative genes including three toll-Interleukin Receptor-nucleotide binding site-leucine rich repeats (TIR-NBS-LRR) genes. However, only one TIR-NBS-LRR appeared to be expressed, and thus constitutes a candidate gene for resistance to P. halstedii race 300.
Weiquan Zhu - One of the best experts on this subject based on the ideXlab platform.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Nyall R London, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Matthew C P SmithAbstract:Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease. Cytokines, the circulating proteins that activate the immune system, also disrupt cell–cell junctions and can trigger tissue oedema and destruction. Using an in vitro human endothelial cell model, this study shows that the disruptive effects of one such cytokine, Interleukin-1 β, are NF-κB independent. Instead they depend on a novel non-canonical pathway involving intracellular GTPases that regulate cadherin trafficking and cell–cell interactions. Targeting of this signalling cascade in an animal model of arthritis prevents cytokine-mediated disruption of endothelial cell barriers and limits tissue damage. The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment1,2,3,4. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response5,6. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell–cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture7,8,9. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88–ARNO–ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
-
Interleukin Receptor activates a myd88 arno arf6 cascade to disrupt vascular stability
Nature, 2012Co-Authors: Weiquan Zhu, Christopher C Gibson, Chadwick T Davis, Zongzhong Tong, Lise K Sorensen, Dallas Shi, Jinping Guo, Nyall London, Matthew C P SmithAbstract:The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as Interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment. Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response. Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture. The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.