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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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The song remains the same： Juvenile Richardson＇s ground squirrels do not respond differentially to mother＇s or colony member＇s alarm calls

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Current Zoology 2012年第5期58卷 773-780页

作者： James F. HARE Kurtis J. warkentin Department of Biological Sciences University of Manitoba Winnipeg MB Canada R3T 2N2 Department of Zoology Brandon University Brandon MB R7A 6A9

Alarm calls are emitted by Richardson＇s ground squirrels Urocitellus richardsonii in response to avian and terrestrial predators. Conspecifics detecting these calls respond with increased vigilance, promoting predator detection and evasion, but in doing so, lose time from foraging. That loss can be minimized if alarm call recipients discriminate among signalers, and weight their response accordingly. For juvenile ground squirrels, we predicted that the trade-off between foraging and vigilance could be optimized via selective response to alarm calls emitted by their own dam, and/or neighboring colony members over calls broad- cast by less familiar conspecifics. Alarm calls of adult female Richardson＇s ground squirrels were elicited in the field using a predator model and recorded on digital audio tape. Free-living focal juveniles were subjected to playbacks of a call of their mother, and on a separate occasion a call from either another adult female from their own colony, or an adult female from another colony. Neither immediate postural responses and escape behavior, nor the duration of vigilance manifested by juveniles differed with exposure to alarm calls of the three adult female signaler types. Thus, juveniles did not respond preferentially to alarm calls emitted by their mothers or colony members, likely reflecting the high cost of ignoring alarm signals where receivers have had limited opportunity to establish past signaler reliability [Current Zoology 58 （5）： 773-780, 2012].

关键词： Alarm Signal Communication Maternal Call Recognition Signal Reliability Ground Squirrel Social Discrimination

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Microstructure evolution in grey cast iron during directional solidification

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International Journal of Minerals,Metallurgy and Materials 2017年第8期24卷 884-890页

作者： Xian-fei Ding Xiao-zheng Li Qiang Feng warkentin Matthias Shi-yao Huang National Center for Materials Service Safety University of Science and Technology Beijing Beijing Key Laboratory of Special Melting and Preparation of High-end Metal University of Science and Technology Beijing State Key Laboratory for Advanced Metals and Materials University of Science and Technology Beijing Ford Research & Advanced Engineering Europe Materials and Process Research Ford Motor Research and Engineering Center

The solidification characteristics and microstructure evolution in grey cast iron were investigated through Jmat-Pro simulations and quenching performed during directional solidification. The phase transition sequence of grey cast iron was determined as L → L + γ→ L + γ + G →γ + G → P(α + Fe_3C) + α + G. The graphite can be formed in three ways: directly nucleated from liquid through the eutectic reaction(L →γ + G), independently precipitated from the oversaturated γ phase(γ→γ + G), and produced via the eutectoid transformation(γ→ G + α). The area fraction and length of graphite as well as the primary dendrite spacing decrease with increasing cooling rate. Type-A graphite is formed at a low cooling rate, whereas a high cooling rate results in the precipitation of type-D graphite. After analyzing the graphite precipitation in the as-cast and transition regions separately solidified with and without inoculation, we concluded that, induced by the inoculant addition, the location of graphite precipitation changes from mainly the γ interdendritic region to the entire γ matrix. It suggests that inoculation mainly acts on graphite precipitation in the γ matrix, not in the liquid or at the solid–liquid front.

关键词： directional solidification grey cast iron phase transition graphite

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The uPA/uPAR system in astrocytic wound healing

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Neural Regeneration Research 2022年第11期17卷 2404-2406页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA

The repair of injured tissue is a highly complex process that involves cell prolife ration,differentiation,and *** migration requires the dismantling of intercellular contacts in the injured zone and their subsequent reconstitution in the wounded ***-type plasminogen activator(u PA)is a serine proteinase found in multiple cell types including endothelial cells,smooth muscle cells,monocytes,and macrophages.A substantial body of experimental evidence with different cell types outside the central nervous system indicates that the binding of uPA to its receptor(uPAR)on the cell surface prompts cell migration by inducing plasmin-mediated degradation of the extracellular *** contrast,although uPA and uPAR are abundantly found in astrocytes and u PA binding to uPAR triggers astrocytic activation,it is unknown if uPA also plays a role in astrocytic *** cadherin is a member of cell adhesion proteins pivotal for the formation of cell-cell conta cts between *** specifically,while the extracellular domain of neuronal cadherin interacts with the extracellular domain of neuronal cadherin in neighboring cells,its intracellular domain binds toβ-catenin,which in turn links the complex to the actin cytos *** synthase kinase 3βis a serine-threonine kinase that prevents the cytoplasmic accumulation ofβ-catenin by inducing its phosphorylation at Ser33,Ser37,and Ser41,thus activating a sequence of events that lead to its proteasomal *** data discussed in this perspective indicate that astrocytes release u PA following a mechanical injury,and that binding of this u PA to uPAR on the cell membrane induces the detachment ofβ-catenin from the intracellular domain of neuronal cadherin by triggering its extracellular signal-regulated kinase 1/2-mediated phosphorylation at ***,this is followed by the cytoplasmic accumulation ofβ-catenin because uPA-induced extracellular signalregulated kinase 1/2 activ

关键词： astrocytes lipoprotein receptor-related protein 6 plasmin urokinase receptor urokinase-type plasminogen activator Wnt-β-catenin pathway wound healing β-catenin

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The plasminogen activating system in the pathogenesis of Alzheimer’s disease

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Neural Regeneration Research 2021年第10期16卷 1973-1977页

作者： manuel Yepes Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor ***’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated ***,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular *** observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain *** plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of ***,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular *** contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβ*** we discuss the role of the PA system in the pathogenesis of AD and

关键词： Alzheimer’s disease amyloid precursor protein amyloidβ neuroserpin plasmin plasminogen activating system plasminogen activator inhibitor-1 synapse tissue-type plasminogen activator urokinase-type plasminogen activator

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Positive curvature, symmetry, and topology

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Frontiers of Mathematics in China 2016年第5期11卷 1099-1122页

作者： manuel AMANN Fakultat fur Mathematik Institut fiir Algebra und Geometrie Karlsruher Institut fiir Technologie Englerstraβe 2 76131 Karlsruhe Germany

We depict recent developments in the field of positive sectional curvature, mainly, but not exclusively, under the assumption of isometric torus actions. After an elaborate introduction to the field, we shall discuss various classification results, before we provide results on the computation of Euler characteristics. This will be the starting point for an examination of more involved invariants and further techniques. In particular, we shall discuss the Hopf conjectures, related decomposition results like the Wilhelm conjecture, results in differential topology and index theory as well as in rational homotopy theory, geometrically formal metrics in positive curvature and much more. The results we present will be discussed for arbitrary dimensions, but also specified to small dimensions. This survey article features mainly depictions of our own work interest in this area and cites results obtained in different collaborations; full statements and proofs can be found in the respective original research articles.

关键词： Positive sectional curvature torus actions Euler characteristic Hopf conjecture index theory Wilhelm conjecture geometric formality

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Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system:implications for neurorepair in the ischemic brain

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Neural Regeneration Research 2020年第4期15卷 620-624页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research Center Department of Neurology Emory University School of Medicine Department of Neurology Veterans Affairs Medical Center

The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of ***,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled ***,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic *** ischemia has a harmful effect on synaptic structure associated with the development of functional *** agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic ***,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic *** plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of ***,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin ***-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and *** role of uPA is the brain is not fully ***,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of ***,following an ischemic injury to the mature brain the expressio

关键词： cerebral ischemia neurorepair plasminogen plasticity stoke synapse urokinase urokinase receptor

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Some Open Problems Related to Creative Telescoping

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Journal of Systems Science & Complexity 2017年第1期30卷 154-172页

作者： CHEN Shaoshi KAUERS manuel Key Laboratory of Mathematics Mechanization Academy of Mathematics and Systems ScienceChinese Academy of Sciences Institute for Algebra J. Kepler University Linz

Creative telescoping is the method of choice for obtaining information about definite sums or integrals. It has been intensively studied since the early 1990s, and can now be considered as a classical technique in computer algebra. At the same time, it is still a subject of ongoing *** paper presents a selection of open problems in this context. The authors would be curious to hear about any substantial progress on any of these problems.

关键词： Computer algebra creative telescoping differential algebra linear operators ore algebras symbolic integration symbolic summation.

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Acoustic streaming and Sun's meridional circulation

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Research in Astronomy and Astrophysics 2016年第9期16卷 101-106页

作者： Jose manuel Valverde Faculty of Physics University of Seville

A vast number of physical processes involving oscillations of a bounded viscous fluid are relevantly influenced by acoustic streaming. When this happens a steady circulation of fluid develops in a thin boundary adjacent to the interface. Some examples are refracted sound waves, a fluid inside a spherical cavity undergoing torsional oscillations or a pulsating liquid droplet. Steady streaming around circular interfaces consists of a hemispherically symmetric recirculation of fluid from the equatorial plane to the polar axes closely resembling the meridional circulation pattern observed in the Sun＇s convection zone that determines the solar cycle. In this paper, it is argued that the acoustic pulsations exhibited by the Sun would lead to acoustic streaming in the boundary of the convection zone. A simple estimation using a typical dominant frequency of 3 mHz and the observed surface oscillation amplitude yields a steady streaming velocity Us - 10 m s^-1, which is on the order of the meridional circulation velocity observed in the Sun＇s convection zone.

关键词： Sun general -- Sun helioseismology -- Sun granulation -- Sun oscillations -- Sun fun-damental parameters -- Sun activity

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Models and observations of sunspot penumbrae

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Science China(Physics,Mechanics & Astronomy) 2009年第11期52卷 1670-1677页

作者： BORRERO Juan manuel Max Planck Institut fr Sonnensystemforschung Max Planck Strasse 2 D 37191 Katlenburg-Lindau Germany

The mysteries of sunspot penumbrae have been under an intense scrutiny for the past 10 years. During this time, some models have been proposed and refuted, while the surviving ones had to be modified, adapted and evolved to explain the ever-increasing array of observational constraints. In this contribution I will review two of the present models, emphasizing their contributions to this field, but also pinpointing some of their inadequacies to explain a number of recent observations at very high spatial resolution (0.32 ). To help explaining these new observations I propose some modifications to each of those models. These modifications bring those two seemingly opposite models closer together into a general picture that agrees well with recent 3D magneto-hydrodynamic simulations.

关键词： sunspots magnetic fields spectropolarimetry magnetohydrodynamics

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