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Beyond the synucleinopathies:alpha synuclein as a driving force in neurodegenerative comorbidities

Translational Neurodegeneration 2019年第1期8卷 346-358页

作者： Naomi P.Visanji anthony e.lang Gabor G.Kovacs edmond J.Safra program in Parkinson’s disease and the Morton and Gloria Shulman Movement disorders clinic Toronto Western HospitalTorontoOntarioCanada Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease University of TorontoTorontoOntarioCanada Laboratory Medicine Program&Krembil Brain Institute University Health NetworkTorontoOntarioCanada

The fundamental role that alpha-synuclein(aSyn)plays in the pathogenesis of neurodegenerative synucleinopathies,including Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy,is a well-accepted fact.A wealth of experimental evidence has linked this relatively small but ubiquitously expressed protein to a plethora of cytopathologic mechanisms and suggests that aSyn may be capable of seeding the progressive spread of synucleinopathy throughout the *** the synucleinopathies,the abnormal deposition of aSyn is frequently seen in a variety of other neurodegenerative proteinopathies including Alzheimer’s *** spite of the fact that the frequency of concomitant aSyn pathology in these disorders is such that it can be considered the rule rather than the exception,the potential role that aSyn may have in these disorders has received relatively little *** this article we postulate that aSyn may in fact be a key protein in driving the pathogenic processes in neurodegenerative *** addition to reviewing the frequency of concomitant deposition of aSyn in the neurodegenerative proteinopathies,we also consider our current understanding of the interaction of aSyn with other neurodegenerative disease-associated proteins,including tau,TDP-43,amyloid-βand prion protein,in the context of neuropathologic studies describing the anatomical sites of potential concomitant *** conclude that a growing body of evidence,encompassing neuropathology studies in human brain,animal models of concomitant proteinopathies and studies employing sophisticated methods of probing protein-protein interaction,cumulatively suggest that aSyn is well positioned to exert a strong influence on the pathogenesis of the neurodegenerative *** hope to stimulate research in this emerging field and consider that future studies exploring the contribution of aSyn to the pathogenic processes in neurodegenerative comorbidities may provide critical

关键词： Amyloid-β Alpha-synuclein Alzheimer’s disease Comorbidity Dementia with Lewy bodies Multiple system atrophy Neurodegeneration Parkinson’s disease Prion protein Progressive supranuclear palsy Proteinopathy Tau TDP-43

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Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes:current and emerging concepts

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Translational Neurodegeneration 2017年第1期6卷 67-91页

作者： Usman Saeed Jordana Compagnone Richard I.Aviv Antonio P.Strafella Sandra e.Black anthony e.lang Mario Masellis Institute of Medical Science Faculty of MedicineUniversity of TorontoTorontoCanada LC Campbell Cognitive Neurology Research Unit Sunnybrook Research InstituteTorontoCanada Department of Medical Imaging University of Toronto and Division of NeuroradiologySunnybrook Health Sciences CentreTorontoCanada Research Imaging Centre Centre for Addiction and Mental HealthTorontoCanada Division of Brain Imaging&Behaviour-Systems NeuroscienceToronto Western HospitalTorontoCanada Division of Neurology Department of MedicineUniversity of TorontoTorontoCanada Heart&Stroke Foundation Canadian Partnership for Stroke Recovery Sunnybrook Health Sciences CentreTorontoCanada Movement Disorders Centre Toronto Western HospitalTorontoCanada edmond J.Safra Program in Parkinson’s Disease University Health NetworkTorontoCanada Cognitive&Movement Disorders Clinic Sunnybrook Health Sciences Centre2075 Bayview Ave.Room A4-55TorontoOntario M4N 3 M5Canada

Two centuries ago in 1817,James Parkinson provided the first medical description of Parkinson’s disease,later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants(also termed,Parkinson-plus syndromes).Today,Parkinson’s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 ***,atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson’s disease,but are uncommon distinct clinicopathological *** of scientific advancements have vastly improved our understanding of these disorders,including improvements in in vivo imaging for biomarker *** imaging for the visualization of structural and functional brain changes is especially important,as it allows a‘window’into the underlying pathophysiological *** this article,we first present an overview of the cardinal clinical and neuropathological features of,1)synucleinopathies:Parkinson’s disease and other Lewy body spectrum disorders,as well as multiple system atrophy,and 2)tauopathies:progressive supranuclear palsy,and corticobasal degeneration.A comprehensive presentation of wellestablished and emerging imaging biomarkers for each disorder are then *** for the following imaging modalities are reviewed:1)structural magnetic resonance imaging(MRI)using T1,T2,and susceptibilityweighted sequences for volumetric and voxel-based morphometric analyses,as well as MRI derived visual signatures,2)diffusion tensor MRI for the assessment of white matter tract injury and microstructural integrity,3)proton magnetic resonance spectroscopy for quantifying proton-containing brain metabolites,4)single photon emission computed tomography for the evaluation of nigrostriatal integrity(as assessed by presynaptic dopamine transporters and postsynaptic dopamine D2 receptors),a

关键词： Biomarkers Parkinson’s disease Atypical parkinsonian syndrome MRI PeT SPeCT Diffusion tensor imaging Molecular imaging Myocardial scintigraphy Transcranial sonography

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Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy

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Translational Neurodegeneration 2022年第1期11卷 845-858页

作者： Ivan Martinez-Valbuena Naomi P.Visanji Ain Kim Heather H.C.Lau Raphaella W.L.So Sohaila Alshimemeri Andrew Gao Michael A.Seidman Maria R.Luquin Joel C.Watts anthony e.lang Gabor G.Kovacs Tanz Centre for Research in Neurodegenerative Diseases University of TorontoTorontoONCanada edmond J.Safra Program in PD and the Morton and Gloria Shulman Movement Disorders Clinic Toronto Western HospitalTorontoONCanada Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Krembil Brain Institute University Health NetworkTorontoONCanada Department of Biochemistry University of TorontoTorontoONCanada Laboratory Medicine Program University Health NetworkTorontoONCanada Department of Neurology Clinica Universidad de NavarraPamplonaNavarraSpain Division of Neurology Department of MedicineKing Saud UniversityRiyadhSaudi Arabia.

Background: Multiple system atrophy (MSA) is a neurodegenerative condition characterized by variable combinations of parkinsonism, autonomic failure, cerebellar ataxia and pyramidal features. Although the distribution of synucleinopathy correlates with the predominant clinical features, the burden of pathology does not fully explain observed differences in clinical presentation and rate of disease progression. We hypothesized that the clinical heterogeneity in MSA is a consequence of variability in the seeding activity of α-synuclein both between different patients and between different brain regions. Methods: The reliable detection of α-synuclein seeding activity derived from MSA using cell-free amplification assays remains challenging. Therefore, we conducted a systematic evaluation of 168 different reaction buffers, using an array of pH and salts, seeded with fully characterized brain homogenates from one MSA and one PD patient. We then validated the two conditions that conferred the optimal ability to discriminate between PD- and MSA-derived samples in a larger cohort of 40 neuropathologically confirmed cases, including 15 MSA. Finally, in a subset of brains, we conducted the first multi-region analysis of seeding behaviour in MSA. Results: Using our novel buffer conditions, we show that the physicochemical factors that govern the in vitro amplification of α-synuclein can be tailored to generate strain-specific reaction buffers that can be used to reliably study the seeding capacity from MSA-derived α-synuclein. Using this novel approach, we were able to sub-categorize the 15 MSA brains into 3 groups: high, intermediate and low seeders. To further demonstrate heterogeneity in α-synuclein seeding in MSA, we conducted a comprehensive multi-regional evaluation of α-synuclein seeding in 13 different regions from 2 high seeders, 2 intermediate seeders and 2 low seeders. Conclusions: We have identified unexpected differences in seed-competent α-synuclein across a coho

关键词： Alpha-synuclein Multiple system atrophy RT-QuIC Seeding behavior

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elderly male with blurry vision

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World Journal of emergency Medicine 2019年第1期10卷 59-60页

作者： anthony Maselli Sarah e.Frasure Department of emergency Medicine Brigham and Women's Hospital

Dear editor,We present a case of an elderly gentleman who was punched in the face and subsequently diagnosed by an emergency physician with acute angle closure glaucoma secondary to a posterior lens *** lamp evaluatio... 详细信息

关键词：小学英语课外阅读阅读材料

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Sanctioned Heterodoxy： Local Cults in Two Chinese Catholic Villages, 1900-Present

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Frontiers of History in China 2016年第1期11卷 42-65页

作者： anthony e. Clark Department ofHistorv Whitworth Universitv. Spokane. WA 99251. USA

While ecclesiastic and state authorities in europe largely abolished medieval cults of saints because of their ＂heterodoxy,＂ late-imperial and modern Chinese Catholic communities in Shanxi still promulgate local cults dedicated to women and men who are believed to have performed posthumous miracles or who represent heroic virtue. Although constrained beneath the scrutiny of imperial, ecclesial, and modern political ideas of ＂orthodoxy＂ and ＂heterodoxy,＂ two Shanxi Catholic villages, Dongergou and Liangquandao （Liuhecun）, have managed to preserve and promote Sister Maria Assunta Pallotta and Father Wang Shiwei as contemporary versions of traditional local cults. One of the manifest characteristics of these two Chinese Catholic local cults is how they have been transformed by traditional Daoist cults and have successfully survived in a liminal space between ＂orthodox＂ and ＂heterodox.＂ Relying on archival materials from the former Taiyuan Catholic Diocese Archive, records held in Roman archives, and oral testimonies, intricate patterns of accommodation and resistance to political and church authorities can be discerned as means for these remote Catholic villages to construct identity and cultivate social cohesion.

关键词： Shanxi Qing Franciscans Maria Assunta Pallotta Wang Shiwei,local Christianity

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Potential distributional shifts in North America of allelopathic invasive plant species under climate change models

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Plant Diversity 2022年第1期44卷 11-19页

作者： Anson Wang anthony e.Melton Douglas eSoltis Pamela SSoltis Department of Biology University of FloridaGainesvilleFL32611USA Florida Museum of Natural History University of FloridaGainesvilleFL32611USA Genetics Institute University of FloridaGainesvilleFL32610USA Biodiversity Institute University of FloridaGainesvilleFL32611USA

Predictive studies play a crucial role in the study of biological invasions of terrestrial plants under possible climate change *** species are recognized for their ability to modify soil microbial communities and influence ecosystem ***,we focused on six species of allelopathic flowering plants-Ailanthus altissima,Casuarina equisetifolia,Centaurea stoebe ***,Dioscorea bulbifera,Lantana camara,and Schinus terebinthifolia-Xhat are invasive in North America and examined their potential to spread further during projected climate *** used Species Distribution Models(SDMs)to predict future suitable areas for these species in North America under several proposed future climate *** and Maxent were used to develop SDMs,estimate current distributions,and predict future areas of suitable climate for each *** with the greatest predicted suitable climate in the future include the northeastern and the coastal northwestern regions of North *** size estimations demonstrate the possibility of extreme range loss for these invasives in the southeastern United States,while new areas may become suitable in the northeastern United States and southeastern *** findings show an overall northward shift of suitable climate during the next few decades,given projected changes in temperature and *** results can be utilized to analyze potential shifts in the distribution of these invasive species and may aid in the development of conservation and management plans to target and control dissemination in areas at higher risk for potential future invasion by these allelopathic species.

关键词： Allelopathy Invasive species Species distribution models ecological niche models Invasion impacts Multi-species assessment

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Steel slag carbonation in a flow-through reactor system:The role of fluid-flux

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Journal of environmental Sciences 2015年第1期27卷 266-275页

作者： eleanor J.Berryman anthony e.Williams-Jones Artashes A.Migdisov Department of earth and Planetary Sciences McGill University Technische Universitat Berlin Los Alamos National Laboratory

Steel production is currently the largest industrial source of atmospheric CO2. As annual steel production continues to grow, the need for effective methods of reducing its carbon footprint increases correspondingly. The carbonation of the calcium-bearing phases in steel slag generated during basic oxygen furnace（BOF） steel production, in particular its major constituent, larnite {Ca2SiO4}, which is a structural analogue of olivine {（MgFe）2SiO4}, the main mineral subjected to natural carbonation in peridotites, offers the potential to offset some of these emissions. However, the controls on the nature and efficiency of steel slag carbonation are yet to be completely understood. experiments were conducted exposing steel slag grains to a CO2–H2O mixture in both batch and flow-through reactors to investigate the impact of temperature, fluid flux, and reaction gradient on the dissolution and carbonation of steel slag. The results of these experiments show that dissolution and carbonation of BOF steel slag are more efficient in a flow-through reactor than in the batch reactors used in most previous studies. Moreover, they show that fluid flux needs to be optimized in addition to grain size, pressure, and temperature, in order to maximize the efficiency of carbonation. Based on these results, a two-stage reactor consisting of a high and a low fluid-flux chamber is proposed for CO2 sequestration by steel slag carbonation,allowing dissolution of the slag and precipitation of calcium carbonate to occur within a single flow-through system.

关键词： CO2sequestration Steel slag carbonation Flow-through reactor Fluid flux

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解析汉娜·阿伦特《人的境况》

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2020年

作者： Sahar Aurore Saeidnia，anthony lang

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THe LIMITATIONS OF LeeD: A CASe STUDY

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Journal of Green Building 2011年第1期6卷 25-33页

作者： anthony S.Denzer Keith e.Hedges University of Wyoming Dept.32951000 E.University AvenueLaramieWY 82071 Hammons School of Architecture Drury University.

The Xanterra houses are situated against the backdrop of one of America’s most spectacular natural landscapes,just a few hundred yards from the north entrance to Yellowstone National *** project consists of two single-family homes for seasonal workers,approximately 2000 square feet *** are mirrored east-to-west but otherwise identical(see Figure 1).The project was completed in 2003,and certified under LeeD-NC v2.0,project#1353 on December 10,2004-the first building project in the National Park system to receive LeeD(Leadership in energy and environmental Design)certification from the USGBC(United States Green Building Council).1 The houses were built with the explicit intent that they would become a model for future green building projects at Yellowstone and other national parks,2 and the project team felt it was fitting that these houses be situated in the nation’s first national ***,they were fundamentally well-designed and constructed,and they incorporated some of the latest technologies for saving energy and water,authentically earning the label“high-performance.”Yet the project only earned the lowest possible rating(“certified”)from LeeD,meaning it is barely considered *** paper documents the green design strategies through the design and construction process,with special attention paid to the influence of the LeeD scorecard on collaborative decision-making and to the difficulties this project encountered during the LeeD assessment *** academic studies have examined the process of LeeD self-reporting and scoring within a professional setting,3 even though contingencies such as common business practices and human limitations clearly affect a project’s LeeD *** paper will show that the LeeD scorecard turned out to be a poor assessment tool in this case study,because the reporting procedure inaccurately reflected the architectural design and ***,there have been a few important papers that conclude that

关键词： LeeD energy modeling insulated concrete passive solar heating construction waste management

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evaluating the biosignature potential of ammonium in Proterozoic red beds and implications for the search for life on Mars

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earth and Planetary Physics 2024年第6期8卷 836-853页

作者： eva e.Stüeken Philip Fralick Stephen Hillier anthony R.Prave School of earth and environmental Sciences University of St AndrewsSt AndrewsKY169TSUK Department of Geology Lakehead UniversityThunder BayON P7B 5E1Canada The James Hutton Institute CraigiebucklerAberdeenAB158QHUK Department of Soil and environment Swedish University of Agricultural Sciences(SLU)SE-75007 UppsalaSweden

Over the past two decades,it has become increasingly apparent that early Mars may once have been warmer,wetter and more habitable for microbial life than it is today,which has spurred discussions about potential biosignatures that may be preserved in Martian *** impediment to this line of research is the pervasive oxidation of Mars’surface due to photochemical oxidants that have likely destroyed remnants of organic ***,we investigate whether nitrogen(N)transferred from biomass to phyllosilicate minerals during diagenesis can be preserved in oxidized *** investigate two sequences of terrestrial Proterozoic red beds,namely the Sibley Group(1.4 Ga)in Canada and the Stoer Group(1.2 Ga)in Scotland,and we find enrichments in authigenic N in the range of several tens of ppm in both *** highest concentrations(ca.100 ppm on average)are found in the most desiccated red beds of the Stoer Group,concurrent with enrichments in potassium(K).We discuss similarities and differences between the two sets of rocks with regards to salinity,pH,biological productivity and K-metasomatism,and we conclude that the ideal mechanism for the preservation of biogenic N in red beds may be in-situ release of ammonium from microbial mats into the clay substrate,possibly facilitated by early diagenetic,biologically induced *** and smectite have been observed on Mars,and experiments suggest that Martian waters contained moderate amounts of dissolved ***,it is conceivable that a similar K and N enrichment process could have occurred as to what we document for the Proterozoic,preserving evidence of life that may have survived to the modern day.

关键词： red beds biosignature Mars nitrogen ammonium clay minerals

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