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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

New species in Aspergillus section Fumigati from reclamation sites in Wyoming (U.s.A.) and revision of A. viridinutans complex

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Fungal Diversity 2014年第1期64卷 253-274页

作者： alena Nováková Vit Hubka Zuzana Dudová Tetsuhiro Matsuzawa alena Kubátová Takashi Yaguchi Miroslav Kolařík Biology Centre As CR v.v.i.Institute of Soil BiologyNa Sádkách 737005ČeskéBudějoviceCzech Republic Laboratory of Physiology and Genetics of Fungi Institute of Microbiology AS CRv.v.iVídeňská108314220 Prague 4Czech Republic Department of Botany Faculty of ScienceCharles University in PragueBenátská212801 Prague 2Czech Republic Medical Mycology Research Center Chiba University1-8-1InohanaChuo-kuChiba 260-8673Japan

The Aspergillus viridinutans complex includes morphologically similar,soil-inhabiting *** its species boundaries have not been fully defined,many isolates from the complex have been isolated as opportunistic human and animal *** the present study,these species were dominant in spoil sites subjected to various types of reclamation management after coal *** species were characterised using two different PCR-fingerprinting methods,sequence data from the β-tubulin(benA)and calmodulin(caM)genes,macro-and micromorphology(optical and scanning electron microscopy),maximum growth temperatures and mating *** addition,RNA polymerase II gene(RPB2),actin(act1)and ITs sequences were deposited for the ex-type isolates of newly described *** mating experiment results,phylogenetic analyses and ascospore morphology suggested the presence of five species in the *** *** aureolus(*** aureola)was the only homothallic *** species,***,***(***)and *** ***.,were heterothallic and their morphologically distinguishable teleomorph was induced by systematic mating *** viridinutans *** to be a very rare species and was represented only by the ex-type isolate in which the MAT1-1 locus was *** viridinutans and *** were typified in accordance with the rules of the new botanical *** species outside the *** complex isolated from the reclamation sites were *** and *** as well as two new sister species,*** *** *** *** were closely related each to other and to *** new species are phylogenetically distant from all anamorphic species and resemble ***,*** and *** in micromorphology and are distinguishable from each other by the slower growth of *** on all tested ***,no isolate from the

关键词： Aspergillus fumigatus Heterothallic species MAT locus Neosartorya udagawae PCR fingerprinting soil fungi

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

Microglial dysfunction and genetic risk for neurodegenerative disease

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Neural Regeneration Research 2025年第5期20卷 1401-1402页

作者： Debra s.MacDonald Jay Penney Department of Biomedical sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations *** tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com *** troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

关键词： degenerative diseases

Results of the Main Phase of Ion separation in the Process of Plasma-Optical Mass separation

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Plasma science and Technology 2015年第10期17卷 862-868页

作者： V.M.BARDAKOV s.D.IVANOV A.V.kazantsev N.A.sTROKIN Institute for Physics and Technology Irkutsk State Technical University

This paper presents separation results of a mixture of nitrogen, argon and krypton ions in the process of plasma-optical mass separation on the POMs-E-3 separator model. We determined the behavior of the separation with a change in the value of magnetic field induction in the azimuthator and in the degree of compensation of the spatial charge in ion flows. An analysis is performed for experimental data by correlation with the results of a theoretical study and numerical experiments. The objectives of future experiments are outlined.

关键词： plasma-optical mass separation plasma accelerator trajectories spatial charge

Intrumer:A Multi Module Distributed Explainable IDs/IPs for securing Cloud Environment

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Computers, Materials & Continua 2025年第1期82卷 579-607页

作者： Nazreen Banu A s.K.B.sangeetha Department of Computer science and Engineering SRM Institute of Science and TechnologyVadapalani CampusChennai600026Tamil NaduIndia

The increasing use of cloud-based devices has reached the critical point of cybersecurity and unwanted network *** environments pose significant challenges in maintaining privacy and *** approaches,such as IDs,have been developed to tackle these ***,most conventional Intrusion Detection system(IDs)models struggle with unseen cyberattacks and complex high-dimensional *** fact,this paper introduces the idea of a novel distributed explainable and heterogeneous transformer-based intrusion detection system,named INTRUMER,which offers balanced accuracy,reliability,and security in cloud settings bymultiplemodulesworking together within *** traffic captured from cloud devices is first passed to the TC&TM module in which the Falcon Optimization Algorithm optimizes the feature selection process,and Naie Bayes algorithm performs the classification of *** selected features are classified further and are forwarded to the Heterogeneous Attention Transformer(HAT)*** this module,the contextual interactions of the network traffic are taken into account to classify them as normal or malicious *** classified results are further analyzed by the Explainable Prevention Module(XPM)to ensure trustworthiness by providing interpretable *** the explanations fromthe classifier,emergency alarms are transmitted to nearby IDsmodules,servers,and underlying cloud devices for the enhancement of preventive *** experiments on benchmark IDs datasets CICIDs 2017,Honeypots,and NsL-KDD were conducted to demonstrate the efficiency of the INTRUMER model in detecting network trafficwith high accuracy for different *** outperforms state-of-the-art approaches,obtaining better performance metrics:98.7%accuracy,97.5%precision,96.3%recall,and 97.8%*** results validate the robustness and effectiveness of INTRUMER in securing diverse cloud environments against sophisticated cyber threats.

关键词： Cloud computing intrusion detection system transformers and explainable artificial intelligence(XAI)

Derivative vegetation indices as a new approach in remote sensing of vegetation

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Frontiers of Earth science 2012年第2期6卷 188-195页

作者： svetlana M.KOCHUBEY Taras A.kazantsev Institute of Plant Physiology and Genetics National Academy of Sciences of UkraineKievVasylkivska 31/1703022Ukraine Estonqan University of Life sciences TartuFr.R.Kreutzwaldi 5EE-51014Estonia

This paper focuses on the advantages of derivative vegetation indices over simple reflectance- based indices that are traditionally used for remote sensing of vegetation. The idea of using reflectance derivatives instead of simple reflectance spectra was proposed several decades ago. Despite this, it has not been widely used in monitoring systems because the derivatives lack reliable parameters. In addition, most satellite monitoring systems are not equipped with hyperspectral sensors, which are considered necessary for operating with the reflectance derivatives. Here, we present original data indicating that the chlorophyll-related derivative index D725/D702 we derived can be accurately estimated from a reflectance spectrum of 10 nm resolution that would be suitable for most satellite-based sensors. Furthermore, the index is not sensitive to soil reflectance and can therefore be used for testing of open crops. Presence of blanc reflectance is also unnecessary. Preliminary results of index testing are presented. Perspectives on using this and other derivative indices are discussed.

关键词： derivative vegetation indices remote sensing,vegetation status