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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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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： ramón Pérez-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDis) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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A Probabilistic Trust Model and Control Algorithm to Protect 6G networks against Malicious Data Injection Attacks in Edge Computing Environments

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Computer Modeling in Engineering & sciences 2024年第10期141卷 631-654页

作者： Borja Bordel sánchez ramón a.ca.ria.tomás.robles Department of Computer systems Universidad Politécnica de MadridMadrid28031Spain Department of Geospatial Engineering Universidad Politécnica de MadridMadrid28031Spain

Future 6G communications are envisioned to enable a large catalogue of pioneering *** will range from networked Cyber-Physical systems to edge computing devices,establishing real-time feedback control loops critical for managing Industry 5.0 deployments,digital agriculture systems,and essential *** provision of extensive machine-type communications through 6G will render many of these innovative systems autonomous and *** full automation will enhance industrial efficiency significantly,it concurrently introduces new cyber risks and *** particular,unattended systems are highly susceptible to trust issues:malicious nodes and false information can be easily introduced into control ***,Denialof-service attacks can be executed by inundating the network with valueless *** anomaly detection schemes require the entire transformation of the control software to integrate new steps and can only mitigate anomalies that conform to predefined mathematical *** based on an exhaustive data collection to detect anomalies are precise but extremely *** models,with their limited understanding of mobile networks,can achieve precision rates no higher than 75%.Therefore,more general and transversal protection mechanisms are needed to detect malicious behaviors *** paper introduces a probabilistic trust model and control algorithm designed to address this *** model determines the probability of any node to be *** channels are pruned for those nodes whose probability is below a given *** trust control algorithmcomprises three primary phases,which feed themodel with three different probabilities,which are weighted and ***,anomalous nodes are identified using Gaussian mixture models and clustering ***,traffic patterns are studied using digital Bessel functions and the functional scalar ***,the in

关键词： 6G networks noise injection attacks Gaussian mixture model Bessel function traffic filter Volterra filter

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stochastic Models to Mitigate sparse sensor Attacks in Continuous-Time non-Linear Cyber-Physical systems

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Computers, Materials & Continua 2023年第9期76卷 3189-3218页

作者： Borja Bordel sánchez ramón a.ca.ria.tomás.robles Information Technologies Department Universidad Politécnica de MadridMadrid28031Spain Geospatial Information Department Universidad Politécnica de MadridMadrid28031Spain

Cyber-Physical systems are very vulnerable to sparse sensor *** current protection mechanisms employ linear and deterministic models which cannot detect attacks ***,in this paper,we propose a new non-linear generalized model to describe Cyber-Physical *** model includes unknown multivariable discrete and continuous-time functions and different multiplicative noises to represent the evolution of physical processes and randomeffects in the physical and ***,the digitalization stage in hardware devices is represented *** and most critical sparse sensor attacks are described through a stochastic *** reconstruction and protectionmechanisms are based on aweighted *** probability in data samples is estimated through different indicators commonly employed in non-linear dynamics(such as the Fourier transform,first-return maps,or the probability density function).A decision algorithm calculates the final reconstructed value considering the previous error *** experimental validation based on simulation tools and real deployments is also carried ***,the new technology performance and scalability are *** prove that the proposed solution protects Cyber-Physical systems against up to 92%of attacks and perturbations,with a computational delay below 2.5 *** proposed model shows a linear complexity,as recursive or iterative structures are not employed,just algebraic and probabilistic *** conclusion,the new model and reconstructionmechanism can protect successfully Cyber-Physical systems against sparse sensor attacks,even in dense or pervasive deployments and scenarios.

关键词： Cyber-physical systems sparse sensor attack non-linear models stochastic models security

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Towards Fully secure 5G Ultra-Low Latency Communications: A Cost-security Functions Analysis

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Computers, Materials & Continua 2023年第1期74卷 855-880页

作者： Borja Bordel ramón Alcarria Joaquin Chung Rajkumar Kettimuthu tomás.robles Iván Armuelles Universidad Politecnica de Madrid MadridEspana Argonne national Laboratory LemontILUSA Universidad de Panama PanamaPanama

Future components to enhance the basic,native security of 5G networks are either complex mechanisms whose impact in the requiring 5G communications are not considered,or lightweight solutions adapted to ultrareliable low-latency communications(URLLC)but whose security properties remain under *** different 5G network slices may have different requirements,in general,both visions seem to fall short at provisioning secure URLLC in the *** this work we address this challenge,by introducing cost-security functions as a method to evaluate the performance and adequacy of most developed and employed non-native enhanced security mechanisms in 5G *** categorize those new security components into different groups according to their purpose and deployment *** propose to analyze them in the context of existing 5G architectures using two different ***,using model checking techniques,we will evaluate the probability of an attacker to be successful against each security ***,using analytical models,we will analyze the impact of these security mechanisms in terms of delay,throughput consumption,and ***,we will combine both approaches using stochastic cost-security functions and the PRIsM model checker to create a global *** results are first evidence of how a 5G network that covers and strengthened all security areas through enhanced,dedicated non-native mechanisms could only guarantee secure URLLC with a probability of∼55%.

关键词： 5G networks security analysis secure low latency communications URLLC eMBBC

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Remaking a connection:molecular players involved in post-injury synapse formation

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neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo tomé ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CnC-Center for neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(Cns)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct Cns injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic Cns disorders.

关键词： viable injury instru

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nucleoside modified mRnA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： sheharyar s.Baig Ali n.Ali Arshad Majid sheffield Institute for Translational neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(Vns)and stroke:stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive Vns paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,sTOP-AUsT,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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Green ionic metal-organic frameworks as nanocatalysts for CO_(2)fixation

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nano Research 2025年第1期18卷 260-269页

作者： nuria Martín Miguel Maireles-Porcar Julián sánchez Velandia Belén Altava Francisco G.Cirujano Eduardo García-Verdugo Departamento de Química Inorgánica y Orgánica Universidad Jaume IAv.Sos Baynats/nCastellóde la PlanaCastellón 12071Spain

Co,ni,and Zn iso-reticular coordination polymers of 2,5-dihydroxyterphthalic acid(H_(2)dot)can be rapidly obtained under room temperature and aqueous conditions using either sodium or ammonium hydroxide as the bases to deprotonate the *** use of metal bromides and tetrabutylammonium hydroxide(TBAOH)as the base allows the green synthesis of ionic metal-organic frameworks(MOFs),characterized by X-ray diffraction(XRD),Fourier transform infrared(FTIR),scanning electron microscopy(sEM),thermo gravimetric analysis(TGA),H-nuclear magnetic resonance(nMR),elemental analysis,and X-ray photoelectron spectroscopy(XPs),and employed in the pressure,solvent,and additive-free CO_(2)fixation to epoxides by its cycloaddition to epichlorohydrin,exhibiting a cooperative behavior between the MOF and the ionic liquid formed within the framework,achieving TOns of the confined tetrabutylammonium bromide(TBABr)up to 700.

关键词： metal-organic frameworks(MOFs) ionic liquids heterogeneous catalysis CO_(2)conversion

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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