The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Taeghwan Hyeon - One of the best experts on this subject based on the ideXlab platform.
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Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage
TSINGHUA UNIV PRESS, 2018Co-Authors: Dong Wan Kang, Chi Kyung Kim, Han Gil Jeong, Min Soh, Taeho Kim, In Young Choi, Doyeon Kim, Wookjin Yang, Taeghwan HyeonAbstract:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH. © Tsinghua University Press and Springer-Verlag Berlin Heidelberg 20174
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biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage
Nano Research, 2017Co-Authors: Dong Wan Kang, Chi Kyung Kim, Han Gil Jeong, Min Soh, Taeho Kim, In Young Choi, Doyeon Kim, Wookjin Yang, Taeghwan HyeonAbstract:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.
Francois Guillemot - One of the best experts on this subject based on the ideXlab platform.
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CENPJ cpap regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of ascl1
Nature Communications, 2015Co-Authors: Patricia P Garcez, Javier Diazalonso, Ivan Crespoenriquez, Diogo S Castro, Donald M Bell, Francois GuillemotAbstract:The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that CENPJ, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of CENPJ during cortical development by in utero electroporation knockdown and found that silencing CENPJ in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of CENPJ in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that CENPJ mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in CENPJ.
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CENPJ/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1
Nature communications, 2015Co-Authors: Patricia P Garcez, Diogo S Castro, Donald M Bell, Javier Díaz-alonso, Ivan Crespo-enriquez, Francois GuillemotAbstract:The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that CENPJ, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of CENPJ during cortical development by in utero electroporation knockdown and found that silencing CENPJ in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of CENPJ in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that CENPJ mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in CENPJ.
Aaron F Straight - One of the best experts on this subject based on the ideXlab platform.
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cdk phosphorylation of xenopus laevis m18bp1 promotes its metaphase centromere localization
The EMBO Journal, 2019Co-Authors: Bradley T French, Aaron F StraightAbstract:Abstract Chromosome segregation requires the centromere, the site on chromosomes where kinetochores assemble in mitosis to attach chromosomes to the mitotic spindle. Centromere identity is defined epigenetically by the presence of nucleosomes containing the histone H3 variant CENP‐A. New CENP‐A nucleosome assembly occurs at the centromere every cell cycle during G1, but how CENP‐A nucleosome assembly is spatially and temporally restricted remains poorly understood. Centromere recruitment of factors required for CENP‐A assembly is mediated in part by the three‐protein Mis18 complex (Mis18α, Mis18β, M18BP1). Here, we show that Xenopus M18BP1 localizes to centromeres during metaphase—prior to CENP‐A assembly—by binding to CENP‐C using a highly conserved SANTA domain. We find that Cdk phosphorylation of M18BP1 is necessary for M18BP1 to bind CENP‐C and localize to centromeres in metaphase. Surprisingly, mutations which disrupt the metaphase M18BP1/CENP‐C interaction cause defective nuclear localization of M18BP1 in interphase, resulting in defective CENP‐A nucleosome assembly. We propose that M18BP1 may identify centromeric sites in metaphase for subsequent CENP‐A nucleosome assembly in interphase.
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xenopus laevis m18bp1 directly binds existing cenp a nucleosomes to promote centromeric chromatin assembly
Developmental Cell, 2017Co-Authors: Bradley T French, Charles Limouse, Frederick G Westhorpe, Aaron F StraightAbstract:Summary Vertebrate centromeres are epigenetically defined by nucleosomes containing the histone H3 variant, CENP-A. CENP-A nucleosome assembly requires the three-protein Mis18 complex (Mis18α, Mis18β, and M18BP1) that recruits the CENP-A chaperone HJURP to centromeres, but how the Mis18 complex recognizes centromeric chromatin is unknown. Using Xenopus egg extract, we show that direct, cell-cycle-regulated binding of M18BP1 to CENP-A nucleosomes recruits the Mis18 complex to interphase centromeres to promote new CENP-A nucleosome assembly. We demonstrate that Xenopus M18BP1 binds CENP-A nucleosomes using a motif that is widely conserved except in mammals. The M18BP1 motif resembles a CENP-A nucleosome binding motif in CENP-C, and we show that CENP-C competes with M18BP1 for CENP-A nucleosome binding at centromeres. We show that both CENP-C and M18BP1 recruit HJURP to centromeres for new CENP-A assembly. This study defines cellular mechanisms for recruiting CENP-A assembly factors to existing CENP-A nucleosomes for the epigenetic inheritance of centromeres.
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a cell free cenp a assembly system defines the chromatin requirements for centromere maintenance
Journal of Cell Biology, 2015Co-Authors: Frederick G Westhorpe, Colin J Fuller, Aaron F StraightAbstract:Centromeres are defined by the presence of CENP-A nucleosomes in chromatin and are essential for accurate chromosome segregation. Centromeric chromatin epigenetically seeds new CENP-A nucleosome formation, thereby maintaining functional centromeres as cells divide. The features within centromeric chromatin that direct new CENP-A assembly remain unclear. Here, we developed a cell-free CENP-A assembly system that enabled the study of chromatin-bound CENP-A and soluble CENP-A separately. We show that two distinct domains of CENP-A within existing CENP-A nucleosomes are required for new CENP-A assembly and that CENP-A nucleosomes recruit the CENP-A assembly factors CENP-C and M18BP1 independently. Furthermore, we demonstrate that the mechanism of CENP-C recruitment to centromeres is dependent on the density of underlying CENP-A nucleosomes.
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dual recognition of cenp a nucleosomes is required for centromere assembly
Journal of Cell Biology, 2010Co-Authors: Christopher W Carroll, Kirstin J Milks, Aaron F StraightAbstract:Centromeres contain specialized nucleosomes in which histone H3 is replaced by the histone variant centromere protein A (CENP-A). CENP-A nucleosomes are thought to act as an epigenetic mark that specifies centromere identity. We previously identified CENP-N as a CENP-A nucleosome-specific binding protein. Here, we show that CENP-C also binds directly and specifically to CENP-A nucleosomes. Nucleosome binding by CENP-C required the extreme C terminus of CENP-A and did not compete with CENP-N binding, which suggests that CENP-C and CENP-N recognize distinct structural elements of CENP-A nucleosomes. A mutation that disrupted CENP-C binding to CENP-A nucleosomes in vitro caused defects in CENP-C targeting to centromeres. Moreover, depletion of CENP-C with siRNA resulted in the mislocalization of all other nonhistone CENPs examined, including CENP-K, CENP-H, CENP-I, and CENP-T, and led to a partial reduction in centromeric CENP-A. We propose that CENP-C binds directly to CENP-A chromatin and, together with CENP-N, provides the foundation upon which other centromere and kinetochore proteins are assembled.
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centromere assembly requires the direct recognition of cenp a nucleosomes by cenp n
Nature Cell Biology, 2009Co-Authors: Christopher W Carroll, Lars E T Jansen, Mariana C C Silva, Kristina M Godek, Aaron F StraightAbstract:The histone H3 variant CENP-A specifies centromere identity. CENP-N is the first selective binding partner of CENP-A. Inhibition of CENP-N binding to CENP-A or CENP-N depletion prevents the recruitment of the other CENP proteins involved in centromere assembly.
Chi Kyung Kim - One of the best experts on this subject based on the ideXlab platform.
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Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage
TSINGHUA UNIV PRESS, 2018Co-Authors: Dong Wan Kang, Chi Kyung Kim, Han Gil Jeong, Min Soh, Taeho Kim, In Young Choi, Doyeon Kim, Wookjin Yang, Taeghwan HyeonAbstract:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH. © Tsinghua University Press and Springer-Verlag Berlin Heidelberg 20174
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biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage
Nano Research, 2017Co-Authors: Dong Wan Kang, Chi Kyung Kim, Han Gil Jeong, Min Soh, Taeho Kim, In Young Choi, Doyeon Kim, Wookjin Yang, Taeghwan HyeonAbstract:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles (CeNPs) are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol (PEG) to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood–brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.
Diogo S Castro - One of the best experts on this subject based on the ideXlab platform.
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CENPJ cpap regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of ascl1
Nature Communications, 2015Co-Authors: Patricia P Garcez, Javier Diazalonso, Ivan Crespoenriquez, Diogo S Castro, Donald M Bell, Francois GuillemotAbstract:The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that CENPJ, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of CENPJ during cortical development by in utero electroporation knockdown and found that silencing CENPJ in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of CENPJ in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that CENPJ mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in CENPJ.
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CENPJ/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1
Nature communications, 2015Co-Authors: Patricia P Garcez, Diogo S Castro, Donald M Bell, Javier Díaz-alonso, Ivan Crespo-enriquez, Francois GuillemotAbstract:The proneural factor Ascl1 controls multiple steps of neurogenesis in the embryonic brain, including progenitor division and neuronal migration. Here we show that CENPJ, also known as CPAP, a microcephaly gene, is a transcriptional target of Ascl1 in the embryonic cerebral cortex. We have characterized the role of CENPJ during cortical development by in utero electroporation knockdown and found that silencing CENPJ in the ventricular zone disrupts centrosome biogenesis and randomizes the cleavage plane orientation of radial glia progenitors. Moreover, we show that downregulation of CENPJ in post-mitotic neurons increases stable microtubules and leads to slower neuronal migration, abnormal centrosome position and aberrant neuronal morphology. Moreover, rescue experiments shows that CENPJ mediates the role of Ascl1 in centrosome biogenesis in progenitor cells and in microtubule dynamics in migrating neurons. These data provide insights into genetic pathways controlling cortical development and primary microcephaly observed in humans with mutations in CENPJ.