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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural regeneration research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal Marta Tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTr pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Design and redesign journey of a drug for transthyretin amyloidosis

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Neural regeneration research 2025年第4期20卷 1096-1097页

作者： francisca Pinheiro Salvador Ventura institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTr)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTr amyloidosis(ATTr).ATTr comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTr aggregation,and hereditary ATTr,a dominantly inherited disorder caused by the deposition of one of over 130 TTr genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTr fibrils in the *** hereditary ATTr,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-fAP)or the heart(familial amyloid cardiomyopathy).in rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

关键词： amyloid aggregation senile

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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural regeneration research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría Javier García-Pardo Salvador Ventura institut de Biotecnologia i de Biomedicina(iBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

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Anisotropic modelling of Opalinus Clay behaviour: from triaxial tests to gallery excavation application

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Journal of rock Mechanics and Geotechnical Engineering 2017年第3期9卷 53-66页

作者： francois Bertrand frédéric Collin Université de Liège Département ArGEnCo/Géomécanique Allée de la découverte 9 4000 Liège Belgium f.r.i.a Fonds de la Recherche Scientifique e FNRS Brussels Belgium

Deep repository in geological formations is the preferential solution considered in many countries to manage high-level nuclear wastes. in Switzerland, the Opalinus Clay is a candidate host rock. in this context, in situ and laboratory tests are conducted on Opalinus Clay to demonstrate the feasibility of deep disposal in this argillaceous formation. This paper presents a constitutive model able to fit the experimental data obtained from some triaxial tests conducted by Jahns(2013) on cores from borehole Schlattingen SLA-1. The elasto-plastic behaviour of Opalinus Clay is reproduced thanks to a DruckerPrager model, taking into account the anisotropy behaviour of this sedimentary rock. The objective is to employ a single set of parameters representative of the material. in a second version of the model, the stress-dependence of the elastic properties and damage are taken into account. finally, the parameters calibrated with experimental tests are used to simulate the excavation of a gallery with a second gradient approach.

关键词： Opalinus Clay Schlattingen Constitutive modelling Anisotropy Dilatancy Localisation Tunnel excavation

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Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

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Neural regeneration research 2025年第4期20卷 1101-1102页

作者： Hadley Osman Paul Ashwood Department of Medical Microbiology and immunology and the M.I.N.D.InstituteUniversity of California at DavisSacramentoCAUSA

During pregnancy,maternal immune activation(MiA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing *** has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the *** is characterized by increased repetitive and stereotyped behaviors and decreased *** of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ***,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased *** allergic asthma(MAA),a form of MiA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

关键词： disorders epidemiology fetus

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Tale of mitochondria and mitochondria-associated Er membrane in patient-derived neuronal models of Wolfram syndrome

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Neural regeneration research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry Timothy Barrett Sovan Sarkar i-STEM CECSCorbeil-EssonnesFrance UniversitéParis-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance institute of Cancer and Genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

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A simulation study for a cost-effective PET-like detector system intended to track particles in granular assemblies

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Particuology 2024年第1期84卷 117-125页

作者： Josephine Oppotsch Antonios Athanassiadis Miriam fritsch fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer Matthias Steinke Ulrich Wiedner ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

Since many industrial applications rely on the processing of densely packed and moving granular ma-terial,obtaining bulk internal information on the particle movement inside the reactors is of great *** information can be delivered by Positron Emission Particle Tracking(PEPT).By marking pellets with a positron-emitting radioisotope,the position of these tracer particles can be determined via the time-of-flight differences of the emitted gamma-ray *** current paper proposes a PET-like detector system based on cost-effective organic plastic scintillators instead of the more common but expensive inorganic *** system is currently under construction and was tested for its resolution and efficiency in this simulation *** Monte Carlo simulations and the software toolkit Geant4,three different geometries(an empty glass box,a generic grate system,and a cubic box of 1 m3 completely filled with pellets)were investigated,leading to a spatial resolution in the millimeter range and an efficiency,defined as the ratio of reconstructed decay locations to simulated decays,of 2.7%,1.4%,and 0.3%.

关键词： Positron emission particle tracking Geant4 Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

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A simulation study on spatial and time resolution for a cost-effective positron emission particle tracking system

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Particuology 2024年第5期88卷 312-322页

作者： Josephine Oppotsch Matthias Steinke Miriam fritsch fritz-Herbert Heinsius Thomas Held Nikoline Hilse Viktor Scherer Ulrich Wiedner ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

This work is the second part of a simulation study investigating the processing of densely packed and moving granular assemblies by positron emission particle tracking (PEPT).Since medical positron emission tomography (PET) scanners commonly used for PEPT are very expensive,a PET-like detector system based on cost-effective organic plastic scintillator bars is being developed and tested for its *** this context,the spatial resolution of a resting positron source,a source moving on a freely designed model path,and a particle motion given by a discrete element method (DEM) simulation is studied using Monte Carlo simulations and the software toolkit *** not only extended the simulation and reconstruction to a moving source but also significantly improved the spatial resolution compared to previous work by adding oversampling and iteration to the reconstruction ***,in the case of a source following a trajectory developed from DEM simulations,a very good resolution of about 1 mm in all three directions and an average 3D deviation between simulated and reconstructed events of 2.3 mm could be ***,the resolution for realistic particle motion within the generic grate system (which is the test rig for further experimental studies) is well below the smallest particle *** simulation of the dependence of the reconstruction accuracy on tracer particle location revealed a nearly constant efficiency within the entire detector system,which demonstrates that boundary effects can be neglected.

关键词： Positron emission particle tracking Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

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regression analysis of squeezing-induced hybrid nanofluid flow in Darcy-forchheimer porous medium

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 193-208页

作者： K.MUHAMMAD M.SArfrAZ Department of Humanities and Sciences School of Electrical Engineering and Computer Science National University of Sciences and Technology Department of Mathematics Quaid-i-Azam University

This article presents a mathematical model addressing a scenario involving a hybrid nanofluid flow between two infinite parallel plates. One plate remains stationary, while the other moves downward at a squeezing velocity. The space between these plates contains a Darcy-forchheimer porous medium. A mixture of water-based fluid with gold(Au) and silicon dioxide(Si O2) nanoparticles is formulated. in contrast to the conventional fourier's heat flux equation, this study employs the Cattaneo-Christov heat flux equation. A uniform magnetic field is applied perpendicular to the flow direction, invoking magnetohydrodynamic(MHD) effects. further, the model accounts for Joule heating, which is the heat generated when an electric current passes through the fluid. The problem is solved via NDSolve in MATHEMATiCA. Numerical and statistical analyses are conducted to provide insights into the behavior of the nanomaterials between the parallel plates with respect to the flow, energy transport, and skin *** findings of this study have potential applications in enhancing cooling systems and optimizing thermal management strategies. it is observed that the squeezing motion generates additional pressure gradients within the fluid, which enhances the flow rate but reduces the frictional drag. Consequently, the fluid is pushed more vigorously between the plates, increasing the flow velocity. As the fluid experiences higher flow rates due to the increased squeezing effect, it spends less time in the region between the plates. The thermal relaxation, however, abruptly changes the temperature, leading to a decrease in the temperature fluctuations.

关键词： Nanofluidics

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Neuroinflammation revisited through the microglial lens

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Neural regeneration research 2025年第7期20卷 1989-1990页

作者： renato Socodato João B.relvas institute of research and innovation in Health(i3S)and institute for Molecular and Cell Biology(iBMC) University of PortoPortoPortugal Department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

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