The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Donald E. Olins - One of the best experts on this subject based on the ideXlab platform.
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Nuclear envelope composition determines the ability of neutrophil type cells to passage through micron scale constrictions
Journal of Biological Chemistry, 2013Co-Authors: Ada L. Olins, Monika Zwerger, Donald E. Olins, Harald Herrmann, Amy C Rowat, Diana E Jaalouk, Irwin A Eydelnant, David A WeitzAbstract:Abstract Neutrophils are characterized by their distinct Nuclear Shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of Nuclear Shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huet anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique Nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed Shape of the neutrophil nucleus is less essential.
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an in vitro model for pelger huet anomaly stable knockdown of lamin b receptor in hl 60 cells
Nucleus, 2010Co-Authors: Ada L. Olins, Monika Zwerger, Harald Herrmann, Aurelie Ernst, Donald E. OlinsAbstract:The principal human blood granulocyte (neutrophil) possesses a lobulated and deformable nucleus, important to facilitate rapid egress from blood vessels as these cells migrate to sites of bacterial or fungal infection. This unusual Nuclear Shape is a product of elevated levels of an integral membrane protein of the Nuclear envelope lamin B receptor (LBR) and of decreased amounts of lamin A/C. In humans, a genetic deficiency of LBR produces Pelger-Huet anomaly, resulting in blood neutrophils that exhibit hypolobulated nuclei with redistributed heterochromatin. Structural changes in Nuclear architecture occur during granulopoiesis within bone marrow. The exact mechanisms of this Nuclear Shape change and of heterochromatin redistribution remain largely unknown. As a tool to facilitate analysis of these mechanisms, a stable LBR knockdown subline of HL-60 cells was established. During in vitro granulopoiesis induced with retinoic acid, the LBR knockdown cells retain an ovoid Shaped nucleus with reduced levels of lamin A/C; while, the parent cells develop highly lobulated nuclei. In contrast, macrophage forms induced in LBR knockdown cells by in vitro treatment with phorbol ester were indistinguishable from the parent cells, judged by both Nuclear Shape and attached cell morphology. The capability of differentiation of LBR knockdown HL-60 cells should facilitate a detailed analysis of the molecular relationship between LBR levels, granulocyte Nuclear Shape and heterochromatin distribution.
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cytoskeletal influences on Nuclear Shape in granulocytic hl 60 cells
BMC Cell Biology, 2004Co-Authors: Ada L. Olins, Donald E. OlinsAbstract:During granulopoiesis in the bone marrow, the nucleus differentiates from ovoid to lobulated Shape. Addition of retinoic acid (RA) to leukemic HL-60 cells induces development of lobulated nuclei, furnishing a convenient model system for Nuclear differentiation during granulopoiesis. Previous studies from our laboratory have implicated Nuclear envelope composition as playing important roles in Nuclear Shape changes. Specifically noted were: 1) a paucity of lamins A/C and B1 in the undifferentiated and RA treated cell forms; 2) an elevation of lamin B receptor (LBR) during induced granulopoiesis. The present study demonstrates that perturbation of cytoskeletal elements influences Nuclear differentiation of HL-60 cells. Because of cytotoxicity from prolonged exposure to cytoskeleton-modifying drugs, most studies were performed with a Bcl-2 overexpressing HL-60 subline. We have found that: 1) nocodazole prevents RA induction of lobulation; 2) taxol induces lobulation and microNuclear formation, even in the absence of RA; 3) cytochalasin D does not inhibit RA induced Nuclear lobulation, and prolonged exposure induces Nuclear Shape changes in the absence of RA. The present results, in the context of earlier data and models, suggest a mechanism for granulocytic Nuclear lobulation. Our current hypothesis is that the Nuclear Shape change involves factors that increase the flexibility of the Nuclear envelope (reduced lamin content), augment connections to the underlying heterochromatin (increased levels of LBR) and promote distortions imposed by the cytoskeleton (microtubule motors creating tension in the Nuclear envelope).
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Mutations in the gene encoding the lamin B receptor produce an altered Nuclear morphology in granulocytes (Pelger-Huet anomaly)
Nature genetics, 2002Co-Authors: Katrin Hoffmann, Ada L. Olins, Donald E. Olins, Christine K. Dreger, Leonard D. Shultz, Barbara Lucke, Hartmut Karl, Reinhard Kaps, Dietmar Müller, Amparo VayaAbstract:Pelger-Huet anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal Nuclear Shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy and skeletal abnormalities. Homozygous offspring in an extinct rabbit lineage showed severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortality. Here we show, by carrying out a genome-wide linkage scan, that PHA is linked to chromosome 1q41-43. We identified four splice-site, two frameshift and two nonsense mutations in LBR, encoding the lamin B receptor. The lamin B receptor (LBR), a member of the sterol reductase family, is evolutionarily conserved and integral to the inner Nuclear membrane; it targets heterochromatin and lamins to the Nuclear membrane. Lymphoblastoid cells from heterozygous individuals affected with PHA show reduced expression of the lamin B receptor, and cells homozygous with respect to PHA contain only trace amounts of it. We found that expression of the lamin B receptor affects neutrophil Nuclear Shape and chromatin distribution in a dose-dependent manner. Our findings have implications for understanding Nuclear envelope-heterochromatin interactions, the pathogenesis of Pelger-like conditions in leukemia, infection and toxic drug reactions, and the evolution of neutrophil Nuclear Shape.
Peter Moller - One of the best experts on this subject based on the ideXlab platform.
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Nuclear Shape evolution based on microscopic level densities
Physical Review C, 2017Co-Authors: Daniel Ward, Jorgen Randrup, Peter Moller, B G Carlsson, T Dossing, Sven AbergAbstract:The authors treat the Nuclear Shape evolution as a random walk on a multidimensional potential-energy surface using Shape-dependent microscopic level densities. The resulting fission-fragment mass distributions agree remarkably well with data, and the gradual disappearance of pairing and shell effects with increasing energy is accounted for without additional parameters.
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Nuclear Shape isomers
Atomic Data and Nuclear Data Tables, 2012Co-Authors: Peter Moller, Arnold J Sierk, R Bengtsson, H Sagawa, Takatoshi IchikawaAbstract:We calculate potential-energy surfaces as functions of spheroidal (epsilon(2)), hexadecapole (epsilon(4)), and axial-asymmetry (gamma) Shape coordinates for 7206 nuclei from A = 31 to A = 290. We tabulate the deformations and energies of all minima deeper than 0.2 MeV and of the saddles between all pairs of minima. The tabulation is terminated at N = 160. Our study is based on the FRLDM macroscopic-microscopic model defined in ATOMIC DATA AND Nuclear DATA TABLES [P. Moller, J.R. Nix, W.D. Myers, W.J. Swiatecki, At. Data Nucl. Data Tables 59 (1995) 185]. We also present potential-energy contour plots versus epsilon(2) and gamma for 1224 even-even nuclei in the region studied. We can identify nuclei for which a necessary condition for Shape isomers occurs, namely multiple minima in the calculated potential-energy surface. We find that the vast majority of Nuclear Shape isomers occur in the A = 80 region, the A = 100 region, and in a more extended region centered around Pb-208. A calculated region of Shape isomers that has so far not been extensively explored is the region of neutron-deficient actinides "north-east" of (208)pb. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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brownian Shape motion on five dimensional potential energy surfaces Nuclear fission fragment mass distributions
Physical Review Letters, 2011Co-Authors: Jorgen Randrup, Peter MollerAbstract:: Although Nuclear fission can be understood qualitatively as an evolution of the Nuclear Shape, a quantitative description has proven to be very elusive. In particular, until now, there existed no model with demonstrated predictive power for the fission-fragment mass yields. Exploiting the expected strongly damped character of Nuclear dynamics, we treat the Nuclear Shape evolution in analogy with Brownian motion and perform random walks on five-dimensional fission potential-energy surfaces which were calculated previously and are the most comprehensive available. Test applications give good reproduction of highly variable experimental mass yields. This novel general approach requires only a single new global parameter, namely, the critical neck size at which the mass split is frozen in, and the results are remarkably insensitive to its specific value.
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brownian Shape motion on five dimensional potential energy surfaces Nuclear fission fragment mass distributions
Physical Review Letters, 2011Co-Authors: Jorgen Randrup, Peter MollerAbstract:Although Nuclear fission can be understood qualitatively as an evolution of the Nuclear Shape, a quantitative description has proven to be very elusive. In particular, until now, there existed no model with demonstrated predictive power for the fission-fragment mass yields. Exploiting the expected strongly damped character of Nuclear dynamics, we treat the Nuclear Shape evolution in analogy with Brownian motion and perform random walks on five-dimensional fission potential-energy surfaces which were calculated previously and are the most comprehensive available. Test applications give good reproduction of highly variable experimental mass yields. This novel general approach requires only a single new global parameter, namely, the critical neck size at which the mass split is frozen in, and the results are remarkably insensitive to its specific value.
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global calculation of Nuclear Shape isomers
Physical Review Letters, 2009Co-Authors: Peter Moller, Arnold J Sierk, R Bengtsson, H Sagawa, Takatoshi IchikawaAbstract:To determine which nuclei may exhibit Shape isomerism, we use a well-benchmarked macroscopic-microscopic model to calculate potential-energy surfaces as functions of spheroidal (epsilon(2)), hexadecapole (epsilon(4)), and axial-asymmetry (gamma) Shape coordinates for 7206 nuclei from A=31 to A=290. We analyze these and identify the deformations and energies of all minima deeper than 0.2 MeV. These minima may correspond to characteristic experimentally observable Shape-isomeric states. Shape isomers mainly occur in the A=80 region, the A=100 region, and in an extended region centered around Pb-208. We compare our model to experimental results for Kr isotopes. Moreover, in a plot versus N and Z we show for each of the 7206 nuclei the calculated number of minima. The results reveal one fairly unexplored region of Shape isomerism, which is experimentally accessible, namely the region northeast of Pb-208(82). (Less)
Ada L. Olins - One of the best experts on this subject based on the ideXlab platform.
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Nuclear envelope composition determines the ability of neutrophil type cells to passage through micron scale constrictions
Journal of Biological Chemistry, 2013Co-Authors: Ada L. Olins, Monika Zwerger, Donald E. Olins, Harald Herrmann, Amy C Rowat, Diana E Jaalouk, Irwin A Eydelnant, David A WeitzAbstract:Abstract Neutrophils are characterized by their distinct Nuclear Shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of Nuclear Shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huet anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique Nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed Shape of the neutrophil nucleus is less essential.
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an in vitro model for pelger huet anomaly stable knockdown of lamin b receptor in hl 60 cells
Nucleus, 2010Co-Authors: Ada L. Olins, Monika Zwerger, Harald Herrmann, Aurelie Ernst, Donald E. OlinsAbstract:The principal human blood granulocyte (neutrophil) possesses a lobulated and deformable nucleus, important to facilitate rapid egress from blood vessels as these cells migrate to sites of bacterial or fungal infection. This unusual Nuclear Shape is a product of elevated levels of an integral membrane protein of the Nuclear envelope lamin B receptor (LBR) and of decreased amounts of lamin A/C. In humans, a genetic deficiency of LBR produces Pelger-Huet anomaly, resulting in blood neutrophils that exhibit hypolobulated nuclei with redistributed heterochromatin. Structural changes in Nuclear architecture occur during granulopoiesis within bone marrow. The exact mechanisms of this Nuclear Shape change and of heterochromatin redistribution remain largely unknown. As a tool to facilitate analysis of these mechanisms, a stable LBR knockdown subline of HL-60 cells was established. During in vitro granulopoiesis induced with retinoic acid, the LBR knockdown cells retain an ovoid Shaped nucleus with reduced levels of lamin A/C; while, the parent cells develop highly lobulated nuclei. In contrast, macrophage forms induced in LBR knockdown cells by in vitro treatment with phorbol ester were indistinguishable from the parent cells, judged by both Nuclear Shape and attached cell morphology. The capability of differentiation of LBR knockdown HL-60 cells should facilitate a detailed analysis of the molecular relationship between LBR levels, granulocyte Nuclear Shape and heterochromatin distribution.
-
cytoskeletal influences on Nuclear Shape in granulocytic hl 60 cells
BMC Cell Biology, 2004Co-Authors: Ada L. Olins, Donald E. OlinsAbstract:During granulopoiesis in the bone marrow, the nucleus differentiates from ovoid to lobulated Shape. Addition of retinoic acid (RA) to leukemic HL-60 cells induces development of lobulated nuclei, furnishing a convenient model system for Nuclear differentiation during granulopoiesis. Previous studies from our laboratory have implicated Nuclear envelope composition as playing important roles in Nuclear Shape changes. Specifically noted were: 1) a paucity of lamins A/C and B1 in the undifferentiated and RA treated cell forms; 2) an elevation of lamin B receptor (LBR) during induced granulopoiesis. The present study demonstrates that perturbation of cytoskeletal elements influences Nuclear differentiation of HL-60 cells. Because of cytotoxicity from prolonged exposure to cytoskeleton-modifying drugs, most studies were performed with a Bcl-2 overexpressing HL-60 subline. We have found that: 1) nocodazole prevents RA induction of lobulation; 2) taxol induces lobulation and microNuclear formation, even in the absence of RA; 3) cytochalasin D does not inhibit RA induced Nuclear lobulation, and prolonged exposure induces Nuclear Shape changes in the absence of RA. The present results, in the context of earlier data and models, suggest a mechanism for granulocytic Nuclear lobulation. Our current hypothesis is that the Nuclear Shape change involves factors that increase the flexibility of the Nuclear envelope (reduced lamin content), augment connections to the underlying heterochromatin (increased levels of LBR) and promote distortions imposed by the cytoskeleton (microtubule motors creating tension in the Nuclear envelope).
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Mutations in the gene encoding the lamin B receptor produce an altered Nuclear morphology in granulocytes (Pelger-Huet anomaly)
Nature genetics, 2002Co-Authors: Katrin Hoffmann, Ada L. Olins, Donald E. Olins, Christine K. Dreger, Leonard D. Shultz, Barbara Lucke, Hartmut Karl, Reinhard Kaps, Dietmar Müller, Amparo VayaAbstract:Pelger-Huet anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal Nuclear Shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy and skeletal abnormalities. Homozygous offspring in an extinct rabbit lineage showed severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortality. Here we show, by carrying out a genome-wide linkage scan, that PHA is linked to chromosome 1q41-43. We identified four splice-site, two frameshift and two nonsense mutations in LBR, encoding the lamin B receptor. The lamin B receptor (LBR), a member of the sterol reductase family, is evolutionarily conserved and integral to the inner Nuclear membrane; it targets heterochromatin and lamins to the Nuclear membrane. Lymphoblastoid cells from heterozygous individuals affected with PHA show reduced expression of the lamin B receptor, and cells homozygous with respect to PHA contain only trace amounts of it. We found that expression of the lamin B receptor affects neutrophil Nuclear Shape and chromatin distribution in a dose-dependent manner. Our findings have implications for understanding Nuclear envelope-heterochromatin interactions, the pathogenesis of Pelger-like conditions in leukemia, infection and toxic drug reactions, and the evolution of neutrophil Nuclear Shape.
Amy C Rowat - One of the best experts on this subject based on the ideXlab platform.
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Nuclear envelope composition determines the ability of neutrophil type cells to passage through micron scale constrictions
Journal of Biological Chemistry, 2013Co-Authors: Ada L. Olins, Monika Zwerger, Donald E. Olins, Harald Herrmann, Amy C Rowat, Diana E Jaalouk, Irwin A Eydelnant, David A WeitzAbstract:Abstract Neutrophils are characterized by their distinct Nuclear Shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of Nuclear Shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huet anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique Nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed Shape of the neutrophil nucleus is less essential.
Jorgen Randrup - One of the best experts on this subject based on the ideXlab platform.
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Nuclear Shape evolution based on microscopic level densities
Physical Review C, 2017Co-Authors: Daniel Ward, Jorgen Randrup, Peter Moller, B G Carlsson, T Dossing, Sven AbergAbstract:The authors treat the Nuclear Shape evolution as a random walk on a multidimensional potential-energy surface using Shape-dependent microscopic level densities. The resulting fission-fragment mass distributions agree remarkably well with data, and the gradual disappearance of pairing and shell effects with increasing energy is accounted for without additional parameters.
-
brownian Shape motion on five dimensional potential energy surfaces Nuclear fission fragment mass distributions
Physical Review Letters, 2011Co-Authors: Jorgen Randrup, Peter MollerAbstract:: Although Nuclear fission can be understood qualitatively as an evolution of the Nuclear Shape, a quantitative description has proven to be very elusive. In particular, until now, there existed no model with demonstrated predictive power for the fission-fragment mass yields. Exploiting the expected strongly damped character of Nuclear dynamics, we treat the Nuclear Shape evolution in analogy with Brownian motion and perform random walks on five-dimensional fission potential-energy surfaces which were calculated previously and are the most comprehensive available. Test applications give good reproduction of highly variable experimental mass yields. This novel general approach requires only a single new global parameter, namely, the critical neck size at which the mass split is frozen in, and the results are remarkably insensitive to its specific value.
-
brownian Shape motion on five dimensional potential energy surfaces Nuclear fission fragment mass distributions
Physical Review Letters, 2011Co-Authors: Jorgen Randrup, Peter MollerAbstract:Although Nuclear fission can be understood qualitatively as an evolution of the Nuclear Shape, a quantitative description has proven to be very elusive. In particular, until now, there existed no model with demonstrated predictive power for the fission-fragment mass yields. Exploiting the expected strongly damped character of Nuclear dynamics, we treat the Nuclear Shape evolution in analogy with Brownian motion and perform random walks on five-dimensional fission potential-energy surfaces which were calculated previously and are the most comprehensive available. Test applications give good reproduction of highly variable experimental mass yields. This novel general approach requires only a single new global parameter, namely, the critical neck size at which the mass split is frozen in, and the results are remarkably insensitive to its specific value.
