The Experts below are selected from a list of 154635 Experts worldwide ranked by ideXlab platform
Ram Sasisekharan - One of the best experts on this subject based on the ideXlab platform.
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a single base pair change in 2009 h1n1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral Transmission in ferrets
2011Co-Authors: Akila Jayaraman, Zachary Shriver, Claudia Pappas, Jessica A Belser, Terrence M Tumpey, Rahul Raman, Karthik Viswanathan, Ram SasisekharanAbstract:The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne Transmission studies using the ferret model have shown that the Transmission Efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced Transmission Efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA) to α2→6 sialylated glycan receptors (human receptors). Here we report that a single point mutation (Ile219→Lys; a base pair change) in the glycan receptor-binding site (RBS) of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics) transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and Transmission Efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.
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a single base pair change in 2009 h1n1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral Transmission in ferrets
2011Co-Authors: Akila Jayaraman, Zachary Shriver, Claudia Pappas, Jessica A Belser, Terrence M Tumpey, Rahul Raman, Karthik Viswanathan, Ram SasisekharanAbstract:The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne Transmission studies using the ferret model have shown that the Transmission Efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced Transmission Efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA) to α2→6 sialylated glycan receptors (human receptors). Here we report that a single point mutation (Ile219→Lys; a base pair change) in the glycan receptor-binding site (RBS) of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics) transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and Transmission Efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.
Kalina T Haas - One of the best experts on this subject based on the ideXlab platform.
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pre post synaptic alignment through neuroligin 1 tunes synaptic Transmission Efficiency
2018Co-Authors: Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. SejnowskiAbstract:The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic Transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses Efficiency.
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pre post synaptic alignment through neuroligin tunes synaptic Transmission Efficiency
2017Co-Authors: Eric Hosy, Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. Sejnowski, Daniel Choquet, Olivier ThoumineAbstract:The nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both amplitude and reliability of synaptic Transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic Transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high Efficiency of synaptic responses.
Dolors Grillobosch - One of the best experts on this subject based on the ideXlab platform.
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pre post synaptic alignment through neuroligin 1 tunes synaptic Transmission Efficiency
2018Co-Authors: Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. SejnowskiAbstract:The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic Transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses Efficiency.
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pre post synaptic alignment through neuroligin tunes synaptic Transmission Efficiency
2017Co-Authors: Eric Hosy, Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. Sejnowski, Daniel Choquet, Olivier ThoumineAbstract:The nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both amplitude and reliability of synaptic Transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic Transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high Efficiency of synaptic responses.
Terrence J. Sejnowski - One of the best experts on this subject based on the ideXlab platform.
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pre post synaptic alignment through neuroligin 1 tunes synaptic Transmission Efficiency
2018Co-Authors: Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. SejnowskiAbstract:The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic Transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses Efficiency.
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pre post synaptic alignment through neuroligin tunes synaptic Transmission Efficiency
2017Co-Authors: Eric Hosy, Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. Sejnowski, Daniel Choquet, Olivier ThoumineAbstract:The nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both amplitude and reliability of synaptic Transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic Transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high Efficiency of synaptic responses.
Benjamin Compans - One of the best experts on this subject based on the ideXlab platform.
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pre post synaptic alignment through neuroligin 1 tunes synaptic Transmission Efficiency
2018Co-Authors: Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. SejnowskiAbstract:The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic Transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses Efficiency.
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pre post synaptic alignment through neuroligin tunes synaptic Transmission Efficiency
2017Co-Authors: Eric Hosy, Dolors Grillobosch, Kalina T Haas, Benjamin Compans, Mathieu Letellier, Thomas M Bartol, Terrence J. Sejnowski, Daniel Choquet, Olivier ThoumineAbstract:The nanoscale organization of neurotransmitter receptors relative to pre-synaptic release sites is a fundamental determinant of both amplitude and reliability of synaptic Transmission. How modifications in the alignment between pre- and post-synaptic machineries affect synaptic current properties has only been addressed with computer modeling, and therefore remains hypothetical. Using dual-color single molecule based super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a C-terminal truncated form of NLG1 disrupted this correlation without affecting the intrinsic organization of AMPAR nanodomains. Moreover, this NLG1 dominant-negative mutant significantly shifted the pre-synaptic release machinery from AMPAR synaptic clusters. Electrophysiology and computer modeling show that this physical shift is sufficient to induce a significant decrease in synaptic Transmission. Thus, our results suggest the necessity for synapses to release glutamate in front of AMPAR nanodomains, to maintain a high Efficiency of synaptic responses.
