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A hypothesis for a novel role of RIN1-the modulation of telomerasefunction by the MAPK signaling pathway

BIOCELL 2020年第4期44卷 525-534页

作者： PATRIC HAMBLETON manuel ALEJANDRO barbieri Department of Biological Sciences Florida International UniversityMiami33199USA Biomedical Science Institute Florida International UniversityMiami33199USA Fairchild Tropical Botanic Garden Miami33156USA International Center of Tropical Botany Florida International UniversityMiamiFL33199USA

Cancerous cells display abnormalities in the signal transduction pathways responsible for responding to extracellular growth factors,or *** that alter proteins involved in these types of pathways can lead to inappropriate or unregulated cell growth,and therefore predispose the cell to become *** critical role of the Ras/mitogen-activated protein kinase(MAPK)pathway in transducing growth signals to the interior of the cell and subsequently stimulating cell growth and proliferation is underscored by the fact that roughly one quarter of all human tumors contain mutant forms of Ras proteins.A particular focus on the signaling and membrane trafficking adaptor protein known as Ras interference 1(RIN1)will reveal how this protein can potentially play a significant role in the development of the cancerous phenotype in certain cell *** equal interest is the possible connection between the Ras/MAPK pathway,and subsequent expression and enzymatic activity of telomerase–a key enzyme known to be overexpressed in roughly 85%of all ***1 is a 783 amino acid(84 kDa)cytosolic protein that is involved in key steps of growth factor receptormediated endocytosis and can potentially moderate signaling through the MAPK ***1,with its unique ability to compete directly with Raf for activation by Ras,could potentially influence signaling through more than one of the MAPK *** so,RIN1 may then be able to exert a precise and selective effect on the downstream signal(s)of a MAPK target such as telomerase.

关键词： Cancer Regulation Pathway Telomere

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Anti-lipid droplets accumulation effect of Annona montana(mountain soursop)leaves extract on differentiation of preadipocytes

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BIOCELL 2022年第3期46卷 567-578页

作者： IVY LEUNG MARIA-LUISA VEISAGA MARGARITA ESPINAL WEI ZHANG ROBERT BARNUM manuel ALEJANDRO barbieri Department of Biological Sciences Florida International UniversityMiami33199USA Biomolecular Sciences Institute Florida International UniversityMiami33199USA Fairchild Tropical Botanic Garden Coral Gables33156USA International Center of Tropical Botany Florida International UniversityMiami33199USA

The Annona genus is a member of Annonaceae,one of the largest families of plants across tropical and subtropical *** family has been used in several ethnomedicinal practices to treat a multitude of human ***,the molecular mechanism underlying its effect on the lipid droplet formation and on the expression of adipogenic markers of this plant remain to be *** this study,we examined whether the extracts from the aerial part of Annona montana affect in vitro differentiation of *** our investigations,both mouse embryo fibroblast 3T3-L1 and normal human primary subcutaneous preadipocytes were incubated with Annona montana extracts(-and its subfractions-)and then analyzed on preadipocyte differentiation,lipid content,lipid droplet size and number,the expression of adipogenic-specific transcriptional factors,as well as cell *** our examinations,we found the Annona montana ethyl acetate extract to exhibit a potent inhibitory effect on adipogenesis,without affecting cell survival,in a dose-dependent *** inhibitory effects included a significant decrease in the accumulation of lipid content by both a dramatic reduction of size and number of lipid *** extract strongly attenuated the expression of PPARγand *** also inhibited the expression of CEBPα,FAS,and Akt without influencing Erk1/2 *** findings suggest that specifically,the Annona montana ethyl acetate extract has a prominent inhibitory effect in cellular pathways of adipocyte differentiation by modulating specific gene expression,which is known to perform a pivotal role during adipogenesis.

关键词： Annona montana extracts Phytochemical analysis Adipogenesis Lipid droplets Adipogenic-specific markers

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Anti-proliferative effect of Annona extracts on breast cancer cells

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BIOCELL 2023年第8期47卷 1835-1852页

作者： MARIA-LUISA VEISAGA MARIAM AHUMADA STACY SORIANO LEONARDO ACUNA WEI ZHANG IVY LEUNG ROBERT BARNUM manuel A.barbieri Biomolecular Sciences Institute Florida International UniversityMiami33199USA Department of Biological Sciences Florida International UniversityMiami33199USA Biochemistry Ph.D.Program Florida International UniversityMiami33199USA Fairchild Tropical Botanic Garden Coral Gables33156USA International Center of Tropical Botany Florida International UniversityMiami33199USA

Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer *** study evaluates the effect of *** leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)***:MTT assay was performed to determine the proliferation of cancer *** iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of *** expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with *** leaves hexane ***:*** leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling *** inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of *** also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and ***,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 ***:Our study indicates that *** leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.

关键词： Annona montana Cancer cell lines Apoptosis Anti-proliferative Cell cycle AKT mTOR

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静谧黑白间

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现代装饰（家居） 2014年第12期 60-65页

作者： Anatology Bao-nghi Droste Fanny Richard Florian Kallus Sebastian Schneider House of Hackney &klevering manuel barbieri molo design NikaZupanc Piet Boon Rometti Sylvie Renoux-Editeur Néazoé Simon Stevens Tina Frey 伏平范嘉苑

对设计师而言,黑白色既是一对最简洁、最朴素的色彩,也是最复杂、最神奇的设计元素。黑色沉稳,白色轻灵,虽然不如彩色那么绚丽,却给人一种高贵的气质。以其为基础,加之人类的智慧,展现出别样的魅力与优雅神韵。黑与白的经典搭配褪去了... 详细信息

对设计师而言,黑白色既是一对最简洁、最朴素的色彩,也是最复杂、最神奇的设计元素。黑色沉稳,白色轻灵,虽然不如彩色那么绚丽,却给人一种高贵的气质。以其为基础,加之人类的智慧,展现出别样的魅力与优雅神韵。黑与白的经典搭配褪去了缤纷的色彩,产生简洁、和谐且富有美感的视觉效果,将五彩缤纷、千变万化的繁杂生态概括于一体,将简约风尚化身为低调的奢华,内敛而不失深刻,且历久弥新,令人回味无穷。＂天为阳,地为阴;阳为白,阴为黑。日月交替,阴阳转换。＂古老的谚语,将世间万物归纳到对立统一的黑白之中。黑白本身就是一门艺术,它源远流长,几乎与人类文明同步发展,经历了五千年来的文化沉淀。在迷离的色彩世界中,黑与白以其独有的简洁、单纯、朴素与概括为各个时代的艺术家所青睐。

关键词：色彩世界文化沉淀黑白色灵感来源令人聚酯材料家居饰品系列产品内部填充启瓶器

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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 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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