The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ariberto Fassati - One of the best experts on this subject based on the ideXlab platform.
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Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response.
Cell Reports, 2019Co-Authors: Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J. Pallett, Thomas F. Baumert, Mala K. Maini, Ariberto FassatiAbstract:Summary In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a Fundamental Function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3′ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress.
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Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response
Elsevier, 2019Co-Authors: Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J. Pallett, Thomas F. Baumert, Mala Maini, Ariberto FassatiAbstract:Summary: In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a Fundamental Function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3′ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress. : Schwenzer et. al discovered that oxidative stress induces nuclear import of cytoplasmic tRNAs. The authors found that this pathway is activated during the integrated stress response. tRNA nuclear import was selective to certain tRNA species and may contribute to the changes in protein translation known to protect cells from stress. Keywords: tRNA, retrograde transport, nucleus, oxidative stress, fluorescence in situ hybridization, unfolded protein response, mTOR, REDD1, PK
Angus R Silver - One of the best experts on this subject based on the ideXlab platform.
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sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks
Nature Communications, 2017Co-Authors: Alex N Caycogajic, Claudia Clopath, Angus R SilverAbstract:Pattern separation is a Fundamental Function of the brain. The divergent feedforward networks thought to underlie this computation are widespread, yet exhibit remarkably similar sparse synaptic connectivity. Marr-Albus theory postulates that such networks separate overlapping activity patterns by mapping them onto larger numbers of sparsely active neurons. But spatial correlations in synaptic input and those introduced by network connectivity are likely to compromise performance. To investigate the structural and Functional determinants of pattern separation we built models of the cerebellar input layer with spatially correlated input patterns, and systematically varied their synaptic connectivity. Performance was quantified by the learning speed of a classifier trained on either the input or output patterns. Our results show that sparse synaptic connectivity is essential for separating spatially correlated input patterns over a wide range of network activity, and that expansion and correlations, rather than sparse activity, are the major determinants of pattern separation.
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sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks
bioRxiv, 2017Co-Authors: Alex N Caycogajic, Claudia Clopath, Angus R SilverAbstract:Pattern separation is a Fundamental Function of the brain. Divergent feedforward networks separate overlapping activity patterns by mapping them onto larger numbers of neurons, aiding learning in downstream circuits. However, the relationship between the synaptic connectivity within these circuits and their ability to separate patterns is poorly understood. To investigate this we built simplified and biologically detailed models of the cerebellar input layer and systematically varied the spatial correlation of their inputs and their synaptic connectivity. Performance was quantified by the learning speed of a classifier trained on either the mossy fiber input or granule cell output patterns. Our results establish that the extent of synaptic connectivity governs the pattern separation performance of feedforward networks by counteracting the beneficial effects of expanding coding space and threshold-mediated decorrelation. The sparse synaptic connectivity in the cerebellar input layer provides an optimal solution to this trade-off, enabling efficient pattern separation and faster learning.
Amjad Javed - One of the best experts on this subject based on the ideXlab platform.
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mitotic occupancy and lineage specific transcriptional control of rrna genes by runx2
Nature, 2007Co-Authors: Mohammad Q Hassan, Sayyed K Zaidi, Mario Galindo, Jitesh Pratap, Daniel W Young, Amjad Javed, Xiaoqing YangAbstract:Regulation of ribosomal RNA genes is a Fundamental process that supports the growth of cells and is tightly coupled with cell differentiation. Although rRNA transcriptional control by RNA polymerase I (Pol I) and associated factors is well studied, the lineage-specific mechanisms governing rRNA expression remain elusive1. Runt-related transcription factors Runx1, Runx2 and Runx3 establish and maintain cell identity2, and convey phenotypic information through successive cell divisions for regulatory events that determine cell cycle progression or exit in progeny cells3. Here we establish that mammalian Runx2 not only controls lineage commitment and cell proliferation by regulating genes transcribed by RNA Pol II, but also acts as a repressor of RNA Pol I mediated rRNA synthesis. Within the condensed mitotic chromosomes we find that Runx2 is retained in large discrete foci at nucleolar organizing regions where rRNA genes reside. These Runx2 chromosomal foci are associated with open chromatin, co-localize with the RNA Pol I transcription factor UBF1, and undergo transition into nucleoli at sites of rRNA synthesis during interphase. Ribosomal RNA transcription and protein synthesis are enhanced by Runx2 deficiency that results from gene ablation or RNA interference, whereas induction of Runx2 specifically and directly represses rDNA promoter activity. Runx2 forms complexes containing the RNA Pol I transcription factors UBF1 and SL1, co-occupies the rRNA gene promoter with these factors in vivo, and affects local chromatin histone modifications at rDNA regulatory regions. Thus Runx2 is a critical mechanistic link between cell fate, proliferation and growth control. Our results suggest that lineage-specific control of ribosomal biogenesis may be a Fundamental Function of transcription factors that govern cell fate.
Hagen Schwenzer - One of the best experts on this subject based on the ideXlab platform.
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Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response.
Cell Reports, 2019Co-Authors: Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J. Pallett, Thomas F. Baumert, Mala K. Maini, Ariberto FassatiAbstract:Summary In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a Fundamental Function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3′ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress.
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Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response
Elsevier, 2019Co-Authors: Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J. Pallett, Thomas F. Baumert, Mala Maini, Ariberto FassatiAbstract:Summary: In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a Fundamental Function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3′ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress. : Schwenzer et. al discovered that oxidative stress induces nuclear import of cytoplasmic tRNAs. The authors found that this pathway is activated during the integrated stress response. tRNA nuclear import was selective to certain tRNA species and may contribute to the changes in protein translation known to protect cells from stress. Keywords: tRNA, retrograde transport, nucleus, oxidative stress, fluorescence in situ hybridization, unfolded protein response, mTOR, REDD1, PK
Alex N Caycogajic - One of the best experts on this subject based on the ideXlab platform.
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sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks
Nature Communications, 2017Co-Authors: Alex N Caycogajic, Claudia Clopath, Angus R SilverAbstract:Pattern separation is a Fundamental Function of the brain. The divergent feedforward networks thought to underlie this computation are widespread, yet exhibit remarkably similar sparse synaptic connectivity. Marr-Albus theory postulates that such networks separate overlapping activity patterns by mapping them onto larger numbers of sparsely active neurons. But spatial correlations in synaptic input and those introduced by network connectivity are likely to compromise performance. To investigate the structural and Functional determinants of pattern separation we built models of the cerebellar input layer with spatially correlated input patterns, and systematically varied their synaptic connectivity. Performance was quantified by the learning speed of a classifier trained on either the input or output patterns. Our results show that sparse synaptic connectivity is essential for separating spatially correlated input patterns over a wide range of network activity, and that expansion and correlations, rather than sparse activity, are the major determinants of pattern separation.
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sparse synaptic connectivity is required for decorrelation and pattern separation in feedforward networks
bioRxiv, 2017Co-Authors: Alex N Caycogajic, Claudia Clopath, Angus R SilverAbstract:Pattern separation is a Fundamental Function of the brain. Divergent feedforward networks separate overlapping activity patterns by mapping them onto larger numbers of neurons, aiding learning in downstream circuits. However, the relationship between the synaptic connectivity within these circuits and their ability to separate patterns is poorly understood. To investigate this we built simplified and biologically detailed models of the cerebellar input layer and systematically varied the spatial correlation of their inputs and their synaptic connectivity. Performance was quantified by the learning speed of a classifier trained on either the mossy fiber input or granule cell output patterns. Our results establish that the extent of synaptic connectivity governs the pattern separation performance of feedforward networks by counteracting the beneficial effects of expanding coding space and threshold-mediated decorrelation. The sparse synaptic connectivity in the cerebellar input layer provides an optimal solution to this trade-off, enabling efficient pattern separation and faster learning.
