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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

胶质母细胞瘤的几何形态学分析:一项基于T1增强扫描的MRI研究

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国际医学放射学杂志 2017年第3期 357-357页

作者： P.B.Julián M.G.Alicia M.David a.s.mariano L.Belén A.Elena 王大伟 Laboratory of Mathematical Oncology Edificio Politécnico Institutode Matemática Aplicada a la Ciencia y la IngenieríaUniversidad de Castilla-La Mancha Avenida de Camilo José Cela

摘要背景通过MRI数据进行胶质母细胞瘤的肿瘤体积测量并预测病人预后一直存在争议,胶质母细胞瘤生长的数学模型表明肿瘤的形态特征与其浸润性密切相关。方法基于117例首发胶质母细胞瘤T1增强扫描影像,对肿瘤的体积及形态学参数进行多中... 详细信息

摘要背景通过MRI数据进行胶质母细胞瘤的肿瘤体积测量并预测病人预后一直存在争议,胶质母细胞瘤生长的数学模型表明肿瘤的形态特征与其浸润性密切相关。方法基于117例首发胶质母细胞瘤T1增强扫描影像,对肿瘤的体积及形态学参数进行多中心回顾性研究。对临床变量进行收集、肿瘤分割,测量参数包括:强化方式、坏死、体积、肿瘤最大直径、等效球径度增强宽幅及其他几个强化"边缘"的形态学参数。应用比例风险分析与Kaplan Meier生存曲线进行

关键词：胶质母细胞瘤几何形态学初等数学 MRI T1

Deltas:a new classification expanding Bates's concepts

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Journal of Palaeogeography 2021年第3期10卷 341-355页

作者： Carlos Zavala mariano Arcuri mariano Di Meglio Agustin Zorzano German Otharan Ainara Irastorza Antonela Torresi Dpto.de Geologia Universidad Nacional del Sur(UNS)Bahia BlancaArgentina GCs Argentina sRL Molina Campos 1508000 Bahia BlancaArgentina Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET)Buenos AiresArgentina

Deltas constitute complex depositional systems formed when a land-derived gravity-flow(carrying water and sediments) discharges into a marine or lacustrine standing body of water. However, the complexity of deltaic sedimentary environments has been oversimplified by geoscientists over the years, considering just littoral deltas as the unique possible type of delta in natural systems. Nevertheless, a rational analysis suggests that deltas can be much more complex. In fact, the characteristics of deltaic deposits will depend on a complex interplay between the bulk density of the incoming flow and the salinity of the receiving water body. This paper explores the natural conditions of deltaic sedimentation according to different density contrasts. The rational analysis of deltaic systems allows to recognize three main fields for deltaic sedimentation, corresponding to(1) hypopycnal(2) homopycnal and(3) hyperpycnal delta settings. The hypopycnal delta field represents the situation when the bulk density of the incoming flow is lower than the density of the water in the basin. According to the salinity of the receiving water body, three different types of hypopycnal littoral deltas are recognized: hypersaline littoral deltas(HsLD), marine littoral deltas(MLD), and brackish littoral deltas(BLD). The basin salinity will determine the capacity of the delta for producing effective buoyant plumes, and consequently the characteristics and extension of prodelta *** littoral deltas(HOLD) form when the density of the incoming flow is roughly similar to the density of the water in the receiving basin. This situation is typical of clean bedload-dominated rivers entering freshwater lakes. Delta front deposits are dominated by sediment avalanches. Typical fallout prodelta deposits are absent or poorly developed since no buoyant plumes are generated. Hyperpycnal deltas form when the bulk density of the incoming flow is higher than the density of the water in the receivi

关键词： Deltas Hyperpycnal flows Homopycnal flows Hypopycnal flows Hyperpycnites Turbidites sediment gravity flows Gravity flows

Paul Groussac’s Void:The French Writer and the Argentine Tradition

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Journal of Foreign Languages and Cultures 2021年第2期5卷 39-55,156页

作者： mariano siskind Harvard University

The French-Argentine Paul Groussac embodied a wide range of writerly functions and cultural-political positions within the Argentine cultural field between the 1880s and the 1920s:writer,playwright,chronicler,traveler,literary,art,and music critic,historian,educator,editor,and director of the National Library during 44 *** essay considers his place in the history of Argentine literature looking at two of the many ways in which he inscribed himself in it The first takes up the production and reproduction of the ontological privilege of French identity as a form of legitimization for his public-and often polemic-interventions,through which he sought to establish scholarly-disciplinary practices,protocols,and conventions that would articulate an entire critical field around his own *** second proposes to think his alternatively weak and strong inscriptions in the literary tradition through his own narrative production:his fiction and dramaturgy,travelogues,and biographical *** other words,this essay situates Groussac in an Argentine literary tradition(conceived as an organic and institutionally sanctioned textual corpus)he believed to have founded and established,a selfrepresentation that led Borges to say that Groussac saw himself as“a missionary of Voltaire among the mulattage.”

关键词： universality particularity tradition modernity literary history travel literature

MOHAWK COLLEGE’s NET ZERO ENERGY AND ZERO CARBON BUILDING-A LIVING LAB FOR HIGH EFFICIENCY AND RENEWABLE ENERGY TECHNOLOGIEs IN BUILDINGs

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Journal of Green Building 2020年第1期15卷 187-214页

作者： Rutul Bhavsar Anthony Cupido mariano Arriaga student Energy and Power Innovation CentreMohawk CollegeHamilton OntarioCanada sustainability Research Chair Mohawk CollegeHamilton OntarioCanadatony. General Manager&corresponding author Energy and Power Innovation CentreMohawk CollegeHamilton OntarioCanada

In recent years,large high efficiency and Net-Zero Energy Buildings(NZEB)are becoming a reality that are setting construction and energy benchmarks for the *** part of this significant effort,in 2018,Mohawk College opened the 8,981 m^(2)(96,670 ft2)Joyce Centre for Partnership and Innovation(JCPI)building in Hamilton,Ontario;becoming Canada’s largest NZEB and zero-carbon institutional *** building integrated a high-efficiency design,construction materials,and technologies;as well as renewable energy technologies to significantly reduce its annual energy consumption and greenhouse gas ***,the JCPI building was also designed as a living lab where students,faculty,researchers and industry are able to monitor and validate the performance of this state-of-the-art *** building was designed to have an energy use intensity of 73 kWh/m^(2)·year(0.26 GJ/m^(2)·year);hence,potentially consuming approximately 80%less energy than the average educational service building in *** paper gives an overview of the design criteria and technologies that were considered to achieve this innova-tive building.

关键词： energy efficiency energy use intensity greenhouse gas emissions net zero energy building renewable energy zero carbon building

A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès sylvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber