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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

Goryachkin＇s agricultural mechanics

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Frontiers of Mechanical Engineering 2016年第1期11卷 87-94页

作者： vera CHINENOVA Mathematics and Mechanics Department Lomonosov Moscow StateUniversity Moscow 119992 Russia

The paper contributes to the development of applied mechanics by establishing a new discipline, namely, agricultural mechanics by academician Vasilii Prohorovich Goryachkin （1868-1935） who was an apprentice of Nikolay Yegorovich Zhukovsky and a graduate of the Moscow University （current known as Moscow State University） and the Imperial Higher Technical School.

关键词： theory of mechanisms and machines agricultural machinery engineering agricultural mechanics

Folate Metabolism Interferes with Plant Immunity through 1C Methionine Synthase-Directed Genome-wide DNA Methylation Enhancement

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Molecular Plant 2019年第9期12卷 1227-1242页

作者： Beatriz Gonzalez Pablo vera Instituto de Biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.I.CCiudad Politecnica de la InnovacionEdificio 8EIngeniero Fausto Elios/n.46022 ValenciaSpain

Plants rely on primary metabolism for flexible adaptation to environmental ***,through a combination of chemical genetics and forward genetic studies in Arabidopsis plants,we identified that the essential folate metabolic pathway exerts a salicylic acid-independent negative control on plant *** of the folate pathway promotes enhanced resistance to Pseudom onas syringae DC3000 via activation of a primed immune state in plants,whereas its implementation results in enhanced *** proteomics analysis using immune-defective mutants identified a methionine synthase(METS1),in charge of the synthesis of Met through the folate-dependent 1C metabolism,acting as a nexus between the folate pathway and plant *** of METS1 represses plant immunity and is accompanied by genome-wide global increase in DNA methylation,revealing that imposing a methylation pressure at the genomic level compromises plant *** together,these results indicate that the folate pathway represents a new layer of complexity in the regulation of plant defense responses.

关键词： folate pathway plant immunity methionine DNA methylation

Engineering the Smart Factory

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Chinese Journal of Mechanical Engineering 2016年第6期29卷 1046-1051页

作者： HARRISON Robert vera Daniel AHMAD Bilal Warwick Manufacturing Group University of Warwick

The fourth industrial revolution promises to create what has been called the smart factory. The vision is that within such modular structured smart factories, cyber-physical systems monitor physical processes, create a virtual copy of the physical world and make decentralised decisions. This paper provides a view of this initiative from an automation systems perspective. In this context it considers how future automation systems might be effectively configured and supported through their lifecycles and how integration, application modelling, visualisation and reuse of such systems might be best achieved. The paper briefly describes limitations in current engineering methods, and new emerging approaches including the cyber physical systems （CPS） engineering tools being developed by the automation systems group （ASG） at Warwick Manufacturing Group, University of Warwick, UK.

关键词： index terms--smart factory Industry 4.0 automation systems cyber-physical systems engineering lifecycle

Small size does not restrain frugivory and seed dispersal across the evolutionary radiation of Galapagos lava lizards

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Current Zoology 2019年第4期65卷 353-361页

作者： Sandra HERVIAS-PAREJO Ruben HELENO Beatriz RUMEU Beatriz GUZMAN Pablo VARGAS Jens M. OLESEN Anna TRAVESET Carlos vera Edgar BENAVIDES manuel NOGALES Institut Mediterrani d'Estudis Avanqats (CSIC-UIB) Global Change Research Group Mallorca Balearic Islands Spain Centre for Functional Ecology Department of Life Sciences University of Coimbra Portugal Real Jardin Botanico (CSIC-RJB) Madrid Spain Department of Bioscience Aarhus University Denmark Galapagos National Park Puerto Ayora Santa Cruz Galapagos Ecuador Department of Ecology and Evolutionary Biology Yale University USA lnstituto de Productos Naturales Agrobiologia (CSIC-IPNA) Island Ecology and Evolution Research Group Canary Islands Spain

Frugivory in lizards is often assumed to be constrained by body size;only large individuals are considered capable of consuming fruits, with the potential of acting as seed dispersers. However, only one previous study has tested the correlation of frugivory with body and head size at an archipelago scale across closely related species. All nine lava lizards (Microlophus spp.) were studied on the eleven largest Galapagos islands from 2010 to 2016 to investigate whether frugivory is related to body and head size. We also tested whether fruit abunda nee in flue nces fruit con sumption and explored the effect of seed ingestion on seedling emergence time and percentage. Our results showed that across islands, lava lizards varied considerably in size (64-102 mm in mean snoutvent length) and level of frugivory (1-23%, i.e., percentage of droppings with seeds). However, level of frugivory was only weakly affected by size as fruit consumption was also common among small lizards. Lava lizards consumed fruits throughout the year and factors other than fruit abundance may be more importa nt drivers of fruit selecti on (e.g., fruit size, energy con tent of pulp). From 2,530 droppings, 1,714 seeds of at least 61 plant species were identified, 76% of the species being native to the Galapagos. Most seeds (91%) showed no external structural damage. Seedling emergence time (44 versus 118 days) and percentage (20% versus 12%) were enhanced for lizardingested seeds compared to control (uningested) fruits. De-pulping by lizards (i.e., removal of pulp with potential germi nation inhibitors) might in crease the chances that at least some seeds find suitable recruitment conditi ons. We con eluded that lizards are importa nt seed dispersers throughout the year and across the whole archipelago, regardless of body size.

关键词： Microlophus oceanic islands plant-animal interactions seed disperser size seed dispersal effectiveness seedling emergence

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

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

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

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