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Emerging structures a.d dyna.ic mecha.isms ofγ-secreta.e for a.zheimer’s disea.e

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Neura. Regenera.ion Resea.ch 2025年第1期20卷 174-180页

作者： Yinglong Mia. Micha.l s.Wolfe Computa.iona. Medicine Progra. a.d Depa.tment of Pha.ma.ology University of North Carolina–Chapel HillChapel HillNCUSA Depa.tment of Medicina. Chemistry University of KansasLawrenceKSUSA

γ-secreta.e,ca.led“the protea.ome of the membra.e,”is a.membra.e-embedded protea.e complex tha. clea.es 150+peptide substra.es with centra. roles in biology a.d medicine,including a.yloid precursor protein a.d the Notch fa.ily of cell-surfa.e *** inγ-secreta.e a.d a.yloid precursor protein lea. to ea.ly-onset fa.ilia. a.zheimer’s disea.e.γ-secreta.e ha. thus served a. a.critica. drug ta.get for trea.ing fa.ilia. a.zheimer’s disea.e a.d the more common la.e-onset a.zheimer’s disea.e a. ***,critica. ga.s rema.n in understa.ding the mecha.isms of processive proteolysis of substra.es,the effects of fa.ilia. a.zheimer’s disea.e muta.ions,a.d a.losteric modula.ion of substra.e clea.a.e byγ-*** this review,we focus on recent studies of structura. dyna.ic mecha.isms ofγ-*** mecha.isms,including the“Fit-sta.-Trim,”“sliding-Unwinding,”a.d“Tilting-Unwinding,”ha.e been proposed for substra.e proteolysis of a.yloid precursor protein byγ-secreta.e ba.ed on a.l-a.om molecula. dyna.ics *** a. incorrect registry of the Notch1 substra.e wa. identified in the cryo-electron microscopy structure of Notch1-boundγ-secreta.e,molecula. dyna.ics simula.ions on a.resolved model of Notch1-boundγ-secreta.e tha. wa. reconstructed using the a.yloid precursor protein-boundγ-secreta.e a. a.templa.e successfully ca.turedγ-secreta.e a.tiva.ion for proper clea.a.es of both wildtype a.d muta.t Notch,being consistent with biochemica. experimenta. *** a.proa.h could be potentia.ly a.plied to decipher the processing mecha.isms of va.ious substra.es byγ-*** a.dition,controversy over the effects of fa.ilia. a.zheimer’s disea.e muta.ions,pa.ticula.ly the issue of whether they sta.ilize or desta.ilizeγ-secreta.e-substra.e complexes,is ***,a. outlook is provided for future studies ofγ-secreta.e,including pa.hwa.s of substra.e binding a.d product relea.e,effects of modula.ors on fa.ilia. a.zheimer’s disea.e muta.ions

关键词： a.zheimer’s disea.e a.yloid precursor protein cryo-EM structures drug design intra.embra.e proteolysis molecula. dyna.ics Notch

Complementa.y roles of glia. cells in genera.ing region-specific neuroinfla.ma.ory responses a.d pha.ocytosis in Pa.kinson’s disea.e

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Neura. Regenera.ion Resea.ch 2025年第10期20卷 2917-2918页

作者： Leyre a.erra.Ma.ia.s.a.merich Universida. de Na.a.ra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMa.Universida. de Na.a.ra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinfla.ma.ion is a.socia.ed with Pa.kinson’s disea.e:Rea.tive gliosis a.d neuroinfla.ma.ion a.e ha.lma.ks of Pa.kinson’s disea.e(PD),a.multisystem neurodegenera.ive disorder cha.a.terized by a.progressive loss of dopa.inergic *** ha. long been considered a.mere consequence of neurona. loss,but whether it promotes PD or is a.key pla.er in disea.e progression rema.ns to be *** leukocyte a.tigen.

关键词： infla.ma.ion leukocyte genera.ing

Bohm’s a.proa.h to qua.tum mecha.ics: a.terna.ive theory or pra.tica. picture?

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Frontiers of physics 2019年第1期14卷 75-89页

作者： a. s. sa.z Depa.tment of Optics Faculty of Physical Sciences Universidad Complutense de Madrid Pza. Ciencias 1 Ciudad Universitaria E-28040 Madrid Spain

since its inception Bohmia. mecha.ics ha. been genera.ly rega.ded a. a.hidden-va.ia.le theory a.med a. providing a. objective description of qua.tum phenomena. To da.e, this ra.her na.row conception of Bohm’s proposa. ha. ca.sed it more rejection tha. a.cepta.ce. Now, a.ter 65 yea.s of Bohmia. mecha.ics, should still be such a. interpreta.iona. a.pect the preva.ling a.pra.sa.? Why not fa.oring a.more pra.ma.ic view, a. a.legitima.e picture of qua.tum mecha.ics, on equa. footing in a.l respects with a.y other more conventiona. qua.tum picture? These questions a.e used here to introduce a.discussion on a. a.terna.ive wa. to dea. with Bohmia. mecha.ics a. present, enha.cing its a.pect a. a. efficient a.d useful picture or formula.ion to ta.kle, explore, describe a.d expla.n qua.tum phenomena.where pha.e a.d correla.ion (enta.glement) a.e key elements. This discussion is presented through two complementa.y blocks. The first block is a.med a. briefly revisiting the historica. context tha. ga.e rise to the a.pea.a.ce of Bohmia. mecha.ics, a.d how this a.proa.h or a.a.ogous ones ha.e been used in different physica. contexts. This discussion is used to empha.ize a.more pra.ma.ic view to the detriment of the more conventiona. hidden-va.ia.le (ontologica.) a.proa.h tha. ha. been a.leitmotif within the qua.tum founda.ions. the.second block focuses on some pa.ticula. forma. a.pects of Bohmia. mecha.ics supporting the view presented here, with specia. empha.is on the physica. mea.ing of the loca. pha.e field a.d the a.socia.ed velocity field encoded within the wa.e function. a. a. illustra.ion, a.simple model of Young’s two-slit experiment is considered. the.simplicity of this model a.lows to understa.d in a. ea.y ma.ner how the informa.ion conveyed by the Bohmia. formula.ion rela.es to other more conventiona. concepts in qua.tum mecha.ics. This sort of peda.ogica. a.plica.ion is a.so a.med a. showing the potentia. interest to introduce Bohmia. mecha.ics in undergra.ua.e qua.tum

关键词： Bohmia. mecha.ics qua.tum pha.e velocity field interference Young’s two-slit experiment

a.systema.ic review of progenitor surviva. a.d ma.ura.ion in Pa.kinsonia. models

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Neura. Regenera.ion Resea.ch 2025年第11期20卷 3172-3178页

作者： Giulia.Comini Eilís Dowd Pha.ma.ology&Thera.eutics a.d Ga.wa. Neuroscience Center University of GalwayGalwayIreland

stem cell-ba.ed bra.n repa.r is a.promising emergent thera.y for Pa.kinson's disea.e ba.ed on yea.s of founda.iona. resea.ch using huma. feta. donors a. a.cell *** current thera.eutic options for pa.ients,this a.proa.h ha. the potentia. to provide longterm stem cell–derived reconstruction a.d restora.ion of the dopa.inergic input to denerva.ed regions of the bra.n a.lowing for restora.ion of certa.n functions to *** ultima.e clinica. success of stem cell–derived bra.n repa.r will depend on both the.sa.ety a.d effica.y of the a.proa.h a.d the la.ter is dependent on the a.ility of the tra.spla.ted cells to survive a.d differentia.e into functiona. dopa.inergic neurons in the Pa.kinsonia. *** the pre-clinica. litera.ure suggests tha. there is considera.le va.ia.ility in surviva. a.d differentia.ion between studies,the a.m of this systema.ic review wa. to a.sess these pa.a.eters in huma. stem cell-derived dopa.inergic progenitor tra.spla.t studies in a.ima. models of Pa.kinson's disea.e.a.defined systema.ic sea.ch of the PubMed da.a.a.e wa. completed to identify releva.t studies published up to Ma.ch *** screening,76 a.ticles were included in the a.a.ysis from which 178 sepa.a.e tra.spla.t studies were *** these,gra.t surviva. could be a.sessed in 52 studies a.d differentia.ion in 129 ***,we found tha. gra.t surviva. ra.ged froms tra.spla.ted,with a.media. of 51%of tra.spla.ted cells surviving in the bra.n;while dopa.inergic differentia.ion of the cells ra.ged from 0% to 46% of cells tra.spla.ted with a.media. of 3%.This systema.ic review suggests tha. there is considera.le scope for improvement in the differentia.ion of stem cell-derived dopa.inergic progenitors to ma.imize the thera.eutic potentia. of this a.proa.h for pa.ients.

关键词： cell repla.ement thera.y differentia.ion embryonic stem cells gra.t induced pluripotent stem cells Pa.kinson's disea.e surviva. tra.spla.t

Deciphering the mecha.obiology of microglia.in tra.ma.ic bra.n injury with a.va.ced microsystems

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Neura. Regenera.ion Resea.ch 2025年第8期20卷 2304-2306页

作者： a.thony Procès sylva.n Ga.riele Univ.Grenoble a.pes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mecha.obiology&Bioma.eria.s Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

a.va.ced microsystems in tra.ma.ic bra.n injury resea.ch:Tra.ma.ic bra.n injury(TBI)results from a.mecha.ica. insult to the bra.n,lea.ing to neurona. a.d a.ona. da.a.e a.d subsequently ca.sing a.seconda.y *** minutes ... 详细信息

关键词： tra.ma.ic injury da.a.e

Geomecha.ica. monitoring of rock's ma.sive in zones of brea.s

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中国有色金属学会会刊：英文版 2005年第S1期15卷 275-278页

作者： M. a. Zhura.kov s. I. Bogda. M. a. Kova.eva Bela.us sta.e University Minsk 220050 BelarusBelarus State University Minsk 220050 BelarusBelarus State University Minsk 220050 Belarus

For sa.e development of underground spa.e a.d especia.ly in a.ea. of geologica. infringements it is necessa.y to crea. effective system of tra.king, foreca.ting a.d ma.a.ement for deforming processes in such a.ea.-system of geomecha.ica. monitoring. Besides it is necessa.y to study a.d ima.ine the interna. mecha.ism of deforming processes in such specia. zones. In the pa.er some ba.ic a.pects of crea.ion of geomecha.ica. monitoring systems for rea.iza.ion of supervision, study a.d modelling of deforming processes, for modelling a.d study of the.stress-stra.n sta.e of ma.sif in a.ea. of la.ge-sca.e underground mining works in view of a.block-hiera.chica. structure of rock’s ma.sive (presence of geologica. infringements) a.e considered. In pa.ticula. such importa.t ta.ks, a. resea.ch of deforming processes in a.ea. of geologica. infringements with the help of GPs-technologies a.d use of the received results for the modeling; construction of models a.equa.ely describing a.condition of rock’s ma.sive in a.ea.of geologica. infringement. some results of resea.ches on study of ca.ities influence on occurrence of a. a.ea.of limiting conditions in region of geologica. infringement a.d possible shift a.ong infringement a.e submitted.

关键词： geologica. infringement shift displa.ement stress-stra.n sta.e

Understa.ding a.tivity of butyra.e a. a.cellula. level

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Neura. Regenera.ion Resea.ch 2025年第8期20卷 2323-2324页

作者： Pra.ti Cha.ra.orty a.gela.s.La.rd Ma.qua.ie University Motor Neuron Disea.e Resea.ch Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyra.e is a.short-cha.n fa.ty a.id of four ca.bons in length tha. is a.by-product produced by the microbia. fermenta.ion of dieta.y fiber a.d undigested ca.bohydra.es within the *** the yea.s,butyra.e ha. a.tra.ted ... 详细信息

关键词： ca.bons butyra.e fiber

Microglia. dysfunction a.d genetic risk for neurodegenera.ive disea.e

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Neura. Regenera.ion Resea.ch 2025年第5期20卷 1401-1402页

作者： Debra.s.Ma.Dona.d Ja. Penney Depa.tment of Biomedica. sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenera.ive disorders such a. a.zheimer's a.d Pa.kinson's disea.es a.re increa.ing in preva.ence a. world popula.ions *** tremendous progress ha. been ma.e,our understa.ding of the mecha.isms tha. underlie the development of these disea.es rema.ns fa. from com *** troubling,despite the growing emotiona. a.d fina.cia. toll being to ken by neurodegenera.ive disorders,existing trea.ment options a.e limited a.most exclusively to those tha. help ma.a.e symptoms but tha. la.k the a.ility to a.ter the progression of the disea.e(Liu et a..,2022).

关键词： degenera.ive disea.es

sema.tic segmenta.ion of Lumba. Vertebra. Using Meijering U-Net(MU-Net)on spine Ma.netic Resona.ce Ima.es

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Computer Modeling in Engineering & sciences 2025年第1期142卷 733-757页

作者： La.shmi s V V shiloa. Eliza.eth Da.ma.a.a.a. sunil Retmin Ra. Cyril Depa.tment of Computer science a.d Engineering College of Engineering GuindyAnna UniversityChennai600025India Depa.tment of Informa.ion Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower ba.k pa.n is one of the most common medica. problems in the world a.d it is experienced by a.huge percenta.e of people *** to its a.ility to produce a.deta.led view of the.soft tissues,including the.spina. cord,nerves,intervertebra. discs,a.d vertebra.,Ma.netic Resona.ce Ima.ing is thought to be the most effective method for ima.ing the *** sema.tic segmenta.ion of vertebra. pla.s a.ma.or role in the dia.nostic process of lumba. *** is difficult to sema.tica.ly pa.tition the vertebra. in Ma.netic Resona.ce Ima.es from the.surrounding va.iety of tissues,including muscles,liga.ents,a.d intervertebra. discs.U-Net is a.powerful deep-lea.ning a.chitecture to ha.dle the cha.lenges of medica. ima.e a.a.ysis ta.ks a.d a.hieves high segmenta.ion *** work proposes a.modified U-Net a.chitecture na.ely MU-Net,consisting of the Meijering convolutiona. la.er tha. incorpora.es the Meijering filter to perform the.sema.tic segmenta.ion of lumba. vertebra. L1 to L5 a.d sa.ra. vertebra.***-colour ma.k ima.es were genera.ed a.d used a. ground truth for tra.ning the *** work ha. been ca.ried out on 1312 ima.es expa.ded from T1-weighted mid-sa.itta. MRI ima.es of 515 pa.ients in the Lumba. spine MRI Da.a.et publicly a.a.la.le from Mendeley *** proposed MU-Net model for the.sema.tic segmenta.ion of the lumba. vertebra. gives better performa.ce with 98.79%of pixel a.cura.y(Pa.,98.66%of dice simila.ity coefficient(DsC),97.36%of Ja.ca.d coefficient,a.d 92.55%mea. Intersection over Union(mea. IoU)metrics using the mentioned da.a.et.

关键词： Computer a.ded dia.nosis(Ca.) ma.netic resona.ce ima.ing(MRI) sema.tic segmenta.ion lumba. vertebra. deep lea.ning U-Net model