The Experts below are selected from a list of 885 Experts worldwide ranked by ideXlab platform
Lin Jiang - One of the best experts on this subject based on the ideXlab platform.
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cryo em of full length alpha synuclein reveals fibril polymorphs with a common structural kernel
Nature Communications, 2018Co-Authors: Kevin A Murray, P Sheth, Michael Q Zhang, G Nair, Michael R Sawaya, Woo Shik Shin, David R Boyer, David Eisenberg, Z H Zhou, Lin JiangAbstract:α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 A resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
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cryo em of full length α synuclein reveals fibril polymorphs with a common structural kernel
Nature Communications, 2018Co-Authors: Kevin A Murray, P Sheth, G Nair, Michael R Sawaya, Woo Shik Shin, David R Boyer, David Eisenberg, Z H Zhou, Ming Zhang, Lin JiangAbstract:α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 A resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
Manju L Prasad - One of the best experts on this subject based on the ideXlab platform.
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hierarchical cluster analysis of myoepithelial basal cell markers in adenoid cystic carcinoma and polymorphous low grade adenocarcinoma
Modern Pathology, 2008Co-Authors: Manju L Prasad, Catalin Barbacioru, Yeshwant B Rawal, Omar F Husein, Ping WenAbstract:Distinguishing adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma of the salivary glands is important for their management. We studied the expression of several myoepithelial and basal/stem cell markers (smooth muscle actin, calponin, smooth muscle myosin heavy chain, metallothionein, maspin, and p63) by immunohistochemistry in 23 adenoid cystic carcinoma and 24 polymorphous low-grade adenocarcinoma, to identify the most useful marker or combination of markers that may help their diagnoses. The results were analyzed using hierarchical cluster analysis and χ2 test for trend. We noted diffuse expression of smooth muscle actin in 20 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), calponin in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), smooth muscle myosin heavy chain in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P=0.001), metallothionein in 22 adenoid cystic carcinoma vs eight polymorphous low-grade adenocarcinoma (P<0.001), maspin in 22 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma, and p63 in 21 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma. Hierarchical clustering of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was virtually identical (κ≤0.0035), suggesting no significant advantage to their use in combination than individually. Diffuse smooth muscle actin expression showed the highest accuracy (91.5%) and positive predictive value (95.2%) for adenoid cystic carcinoma. Thus, diffuse expression of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was highly predictive of adenoid cystic carcinoma, whereas maspin and p63 were frequently expressed in both tumors. In differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, smooth muscle actin as a single ancillary test in support of the histological findings, appears to be as efficient as multiple immunohistochemical tests.
Kevin A Murray - One of the best experts on this subject based on the ideXlab platform.
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cryo em of full length alpha synuclein reveals fibril polymorphs with a common structural kernel
Nature Communications, 2018Co-Authors: Kevin A Murray, P Sheth, Michael Q Zhang, G Nair, Michael R Sawaya, Woo Shik Shin, David R Boyer, David Eisenberg, Z H Zhou, Lin JiangAbstract:α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 A resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
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cryo em of full length α synuclein reveals fibril polymorphs with a common structural kernel
Nature Communications, 2018Co-Authors: Kevin A Murray, P Sheth, G Nair, Michael R Sawaya, Woo Shik Shin, David R Boyer, David Eisenberg, Z H Zhou, Ming Zhang, Lin JiangAbstract:α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 A resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
Dominic A Fortes - One of the best experts on this subject based on the ideXlab platform.
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thermal expansion of the al2sio5 polymorphs kyanite andalusite and sillimanite between 10 and 1573 k determined using time of flight neutron powder diffraction
Physics and Chemistry of Minerals, 2019Co-Authors: Dominic A FortesAbstract:Powder and single-crystal diffraction data measured from the three geologically important Al2SiO5 polymorphs, kyanite, andalusite and sillimanite, over the last six decades have given varying accounts of each polymorph’s thermal expansion, the scatter between and even within experimental datasets often being quite large. Furthermore, there are no lattice parameter determinations below 273 K, where the thermodynamic functions vary substantially, and few measurements above 1200 K. Accurate and precise lattice parameters of natural kyanite, andalusite and sillimanite have therefore been obtained in the range 10–1573 K using the high-resolution powder diffractometer (HRPD) at the ISIS neutron spallation source. Accuracy is ensured by the use of an internal standard (NIST silicon SRM640c) and use of a bulk probe (neutrons) to avoid the specimen-displacement corrections required by typical back-reflection X-ray diffraction methods. Precision is ensured by use of the time-of-flight method on one of the longest primary neutron flightpath instruments in the world. For kyanite, the improved precision reveals the true temperature dependence of the three inter-axial angles for the first time, permitting derivation of accurate thermal expansion tensor coefficients. For both andalusite and sillimanite, the measurements reveal hitherto unknown regions of substantial negative linear expansivity below room temperature, along the c-axis in andalusite and along the a-axis in sillimanite. Above 1200 K, sillimanite exhibits an anomalous increase in thermal expansion that may be due to a change in the Al/Si tetrahedral site ordering.
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thermal expansion of the al 2 sio 5 polymorphs kyanite andalusite and sillimanite between 10 and 1573 k determined using time of flight neutron powder diffraction
Pacific Rim Conference on Multimedia, 2019Co-Authors: Dominic A FortesAbstract:Powder and single-crystal diffraction data measured from the three geologically important Al2SiO5 polymorphs, kyanite, andalusite and sillimanite, over the last six decades have given varying accounts of each polymorph’s thermal expansion, the scatter between and even within experimental datasets often being quite large. Furthermore, there are no lattice parameter determinations below 273 K, where the thermodynamic functions vary substantially, and few measurements above 1200 K. Accurate and precise lattice parameters of natural kyanite, andalusite and sillimanite have therefore been obtained in the range 10–1573 K using the high-resolution powder diffractometer (HRPD) at the ISIS neutron spallation source. Accuracy is ensured by the use of an internal standard (NIST silicon SRM640c) and use of a bulk probe (neutrons) to avoid the specimen-displacement corrections required by typical back-reflection X-ray diffraction methods. Precision is ensured by use of the time-of-flight method on one of the longest primary neutron flightpath instruments in the world. For kyanite, the improved precision reveals the true temperature dependence of the three inter-axial angles for the first time, permitting derivation of accurate thermal expansion tensor coefficients. For both andalusite and sillimanite, the measurements reveal hitherto unknown regions of substantial negative linear expansivity below room temperature, along the c-axis in andalusite and along the a-axis in sillimanite. Above 1200 K, sillimanite exhibits an anomalous increase in thermal expansion that may be due to a change in the Al/Si tetrahedral site ordering.
Frank Wurthner - One of the best experts on this subject based on the ideXlab platform.
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single crystal field effect transistors of new cl 2 ndi polymorph processed by sublimation in air
Nature Communications, 2015Co-Authors: Matthias Stolte, Christian Burschka, Nis Hauke Hansen, Thomas Musiol, Daniel Kalblein, Jens Pflaum, Jochen Brill, Xutang Tao, Frank WurthnerAbstract:Physical properties of active materials built up from small molecules are dictated by their molecular packing in the solid state. Here we demonstrate for the first time the growth of n-channel single-crystal field-effect transistors and organic thin-film transistors by sublimation of 2,6-dichloro-naphthalene diimide in air. Under these conditions, a new polymorph with two-dimensional brick-wall packing mode (β-phase) is obtained that is distinguished from the previously reported herringbone packing motif obtained from solution (α-phase). We are able to fabricate single-crystal field-effect transistors with electron mobilities in air of up to 8.6 cm2 V−1 s−1 (α-phase) and up to 3.5 cm2 V−1 s−1 (β-phase) on n-octadecyltriethoxysilane-modified substrates. On silicon dioxide, thin-film devices based on β-phase can be manufactured in air giving rise to electron mobilities of 0.37 cm2 V−1 s−1. The simple crystal and thin-film growth procedures by sublimation under ambient conditions avoid elaborate substrate modifications and costly vacuum equipment-based fabrication steps. Charge transport in organic semiconductors is highly sensitive to crystalline polymorphs. Here, He et al. manufacture the first n-channel single-crystal transistor via sublimation at ambient conditions and identify a new polymorphous phase that does not exist in its solution-processed counterpart.
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single crystal field effect transistors of new cl 2 ndi polymorph processed by sublimation in air
Nature Communications, 2015Co-Authors: Tao He, Matthias Stolte, Christian Burschka, Nis Hauke Hansen, Thomas Musiol, Daniel Kalblein, Jens Pflaum, Jochen Brill, Frank WurthnerAbstract:Charge transport in organic semiconductors is highly sensitive to crystalline polymorphs. Here, He et al. manufacture the first n-channel single-crystal transistor via sublimation at ambient conditions and identify a new polymorphous phase that does not exist in its solution-processed counterpart.
