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- Gou, De Hai, et al.
(author)
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Inhibition of copper transporter 1 prevents α-synuclein pathology and alleviates nigrostriatal degeneration in AAV-based mouse model of Parkinson's disease
- 2021
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In: Redox Biology. - : Elsevier BV. - 2213-2317. ; 38
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Journal article (peer-reviewed)abstract
- The formation of α-synuclein aggregates is a major pathological hallmark of Parkinson's disease. Copper promotes α-synuclein aggregation and toxicity in vitro. The level of copper and copper transporter 1, which is the only known high-affinity copper importer in the brain, decreases in the substantia nigra of Parkinson's disease patients. However, the relationship between copper, copper transporter 1 and α-synuclein pathology remains elusive. Here, we aim to decipher the molecular mechanisms of copper and copper transporter 1 underlying Parkinson's disease pathology. We employed yeast and mammalian cell models expressing human α-synuclein, where exogenous copper accelerated intracellular α-synuclein inclusions and silencing copper transporter 1 reduced α-synuclein aggregates in vitro, suggesting that copper transporter 1 might inhibit α-synuclein pathology. To study our hypothesis in vivo, we generated a new transgenic mouse model with copper transporter 1 conditional knocked-out specifically in dopaminergic neuron. Meanwhile, we unilaterally injected adeno-associated viral human-α-synuclein into the substantia nigra of these mice. Importantly, we found that copper transporter 1 deficiency significantly reduced S129-phosphorylation of α-synuclein, prevented dopaminergic neuronal loss, and alleviated motor dysfunction caused by α-synuclein overexpression in vivo. Overall, our data indicated that inhibition of copper transporter 1 alleviated α-synuclein mediated pathologies and provided a novel therapeutic strategy for Parkinson's disease and other synucleinopathies.
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- Ding, Xue Bing, et al.
(author)
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Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
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Journal article (peer-reviewed)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
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- Han, Xin-Bao, et al.
(author)
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Ultrasmall Abundant Metal-Based Clusters as Oxygen-Evolving Catalysts
- 2019
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:1, s. 232-239
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Journal article (peer-reviewed)abstract
- The oxygen evolution reaction is a crucial step in water electrolysis to develop clean and renewable energy. Although noble metal-based catalysts have demonstrated high activity for the oxygen evolution reaction, their application is limited by their high cost and low availability. Here we report the use of a molecule-to-cluster strategy for preparing ultrasmall trimetallic clusters by using the polyoxometalate molecule as a precursor. Ultrafine (0.8 nm) transition-metal clusters with controllable chemical composition are obtained. The transition-metal clusters enable highly efficient oxygen evolution through water electrolysis in alkaline media, manifested by an overpotential of 192 mV at 10 mA cm–2, a low Tafel slope of 36 mV dec–1, and long-term stability for 30 h of electrolysis. We note, however, that besides the excellent performance as an oxygen evolution catalyst, our molecule-to-cluster strategy provides a means to achieve well-defined transition-metal clusters in the subnanometer regime, which potentially can have an impact on several other applications.
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- Schuettpelz, Eric, et al.
(author)
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A community-derived classification for extant lycophytes and ferns
- 2016
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In: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
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Journal article (peer-reviewed)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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7. |
- Sun, Xiaoyu, et al.
(author)
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Revealing microstructural degradation mechanism induced by interdiffusion between Amdry365 coating and IN792 superalloy
- 2024
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In: Materials and Design. - : ELSEVIER SCI LTD. - 1873-4197 .- 0264-1275. ; 241
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Journal article (peer-reviewed)abstract
- Metallic coatings are widely employed to improve the oxidation resistance of superalloys. However, the interdiffusion between the metallic coatings and the superalloys leads to microstructural degradation in both. Some of the underlying degradation mechanisms are still elusive, e.g., the γ′ (Ni3Al) phase depletion in superalloys, where a large amount of γ′ precipitates are dissolved in the γ matrix even though the incoming Al from coatings indeed increases the Al content. Here, we investigated the interdiffusion behavior between the Amdry365 coating and the IN792 superalloy at 1100 °C, using multiple microscopic techniques and thermodynamics calculations. Our results showed an excellent agreement between experiments and thermodynamics simulations, indicating the dominant role of Al on the initial diffusion-induced phase transitions. We proposed the Al-Cr interference effect to account for the pile-up behavior of Cr and the reduced Al content near the coating/superalloy interface. The local phase equilibrium calculations revealed that the γ′ depletion in the superalloy is primarily attributed to the loss of γ′-forming elements, such as Ta and Ti. Our findings opened up an avenue for studies on the superalloy/coating interdiffusion, contributing to reducing this damaging impact.
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- Ai-Xi, Chen, et al.
(author)
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Potential-Induced Phase Transition of N-Isobutyryl-L-cysteine Monolayers on Au(111) Surfaces
- 2017
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In: Wuli huaxue xuebao. - : PEKING UNIV PRESS. - 1000-6818. ; 33:5, s. 1010-1016
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Journal article (peer-reviewed)abstract
- Functional solid substrates modified by self-assembled monolayers (SAMs) have potential applications in biosensors, chromatography, and biocompatible materials. The potential-induced phase transition of N-isobutyryl-L-cysteine (L-NIBC) SAMs on Au(111) surfaces was investigated by in-situ electrochemical scanning tunneling microscopy (EC-STM) in 0.1 mol.L-1 H2SO4 solution. The NIBC SAMs with two distinct structures (alpha phase and beta phase) can be prepared by immersing the Au(111) substrate in pure NIBC aqueous solution and NIBC solution controlled by phosphate buffer at pH 7, respectively. The as-prepared a phase and beta phase of NIBC SAMs show various structural changes under the control of electrochemical potentials of the Au(111) in H2SO4 solution. The a phase NIBC SAMs exhibit structural changes from ordered to disordered structures with potential changes from 0.7 V (vs saturated calomel electrode, SCE) to 0.2 V. However, the beta phase NIBC SAMs undergo structural changes from disordered structures (E < 0.3 V) to y phase (0.4 V < E < 0.5 V) and finally to the beta phase (0.5 V < E < 0.7 V). EC-STM images also indicate that the phase transition from the alpha phase NIBC SAMs to the a phase occurs at positive potential. Combined with density functional theory (DFT) calculations, the phase transition from the beta phase to the a phase is explained by the potential-induced break of bonding interactions between -COO- and the negatively charged gold surfaces.
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- An, Junghwa, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Journal article (peer-reviewed)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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- Aranke, Omkar, 1994-, et al.
(author)
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Microstructural Evolution and Sintering of Suspension Plasma-Sprayed Columnar Thermal Barrier Coatings
- 2019
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In: Journal of thermal spray technology (Print). - : Springer Science and Business Media LLC. - 1059-9630 .- 1544-1016. ; 28:1-2, s. 198-211
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Journal article (peer-reviewed)abstract
- Suspension plasma spray (SPS) is capable of producing coatings with porous columnar structure, and it is also a much cheaper process compared to the conventionally used electron beam physical vapor deposition (EB-PVD). Although TBCs with a columnar microstructure that are fabricated using SPS have typically lower thermal conductivity than EB-PVD, they are used sparingly in the aerospace industry due to their lower fracture toughness and limited lifetime expectancy. Lifetime of TBCs is highly influenced by the topcoat microstructure. The objective of this work was to study the TBCs produced using axial SPS with different process parameters. Influence of the microstructure on lifetime of the coatings was of particular interest, and it was determined by thermal cyclic fatigue testing. The effect of sintering on microstructure of the coatings exposed to high temperatures was also investigated. Porosity measurements were taken using image analysis technique, and thermal conductivity of the coatings was determined by laser flash analysis. The results show that axial SPS is a promising method of producing TBCs having various microstructures with good lifetime. Changes in microstructure of topcoat due to sintering were seen evidently in porous coatings, whereas dense topcoats showed good resistance against sintering.
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